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Trial record 23 of 439 for:    Methylphenidate

Methylphenidate Treatment of Attention Deficits in Epilepsy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02178995
Recruitment Status : Completed
First Posted : July 1, 2014
Results First Posted : August 31, 2016
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
Kimford Jay Meador, Stanford University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Epilepsy
Cognitive Deficits
Attention Deficits
Intervention Drug: Methylphenidate
Enrollment 55
Recruitment Details Participants were enrolled primarily through the Stanford Neurology and Neuropsychiatry clinics between August 2014 and July 2015.
Pre-assignment Details 4 participants signed their consent form, but did not complete any study visits and therefore produced no study data. Therefore, 55 participants are 'enrolled,' but only 51 actually participated in the study flow.
Arm/Group Title Participants With Epilepsy (Open-label) Healthy Controls 10mg, 20mg, Then Placebo (Double-blind) 10mg, Placebo, Then 20mg (Double-blind) Placebo, 20mg, Then 10mg (Double-blind Placebo, 10mg, Then 20mg (Double-blind) 20mg, Placebo, Then 10mg (Double-blind) 20mg, 10mg, Then Placebo - Double-blind 40mg, 20mg, Then Placebo (One Participant)
Hide Arm/Group Description Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After a four week treatment trial, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

This study was originally intended to use 40mg, 20mg, and placebo doses rather than 20mg, 10mg, and placebo. This individual developed tachycardia (see adverse events) on the 40mg dose, and was withdrawn from the double-blind portion as a result. We removed the 40mg doses from this study and replaced them with 10mg doses. No other participant received a 40mg dose. This participant rejoined the open-label portion after consultation with his PCP due to significant perceived benefit from the MPH dose.
Period Title: Double Blind
Started 0 16 5 6 6 6 5 6 1
Completed 0 15 5 6 6 5 5 4 0
Not Completed 0 1 0 0 0 1 0 2 1
Reason Not Completed
Adverse Event             0             0             0             0             0             1             0             1             1
Lost to Follow-up             0             1             0             0             0             0             0             1             0
Period Title: Open Label
Started 30 [1] 14 [2] 0 0 0 0 0 0 0
Completed 28 14 0 0 0 0 0 0 0
Not Completed 2 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             2             0             0             0             0             0             0             0             0
[1]
2 declined to join open-label. 1 withdrew from double-blind but rejoined open-label due to benefit.
[2]
One was lost to follow-up after completion of visit 4.
Arm/Group Title Participants With Epilepsy Healthy Controls Total
Hide Arm/Group Description

Participants received three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time. Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After four weeks, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication. Total of all reporting groups
Overall Number of Baseline Participants 35 16 51
Hide Baseline Analysis Population Description
Total number of individuals who signed consents = 55. 4 of these individuals with epilepsy signed their consent but did not follow through and participate in the study. The remaining 51 (35 epilepsy, 16 controls) are represented here.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 35 participants 16 participants 51 participants
37
(20 to 64)
45
(22 to 62)
39.5
(20 to 64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 16 participants 51 participants
Female
19
  54.3%
10
  62.5%
29
  56.9%
Male
16
  45.7%
6
  37.5%
22
  43.1%
Mean years of education  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 35 participants 16 participants 51 participants
15
(12 to 20)
15
(12 to 18)
15
(12 to 20)
Mean duration of epilepsy  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 35 participants 16 participants 51 participants
12.5
(1 to 41)
0
(0 to 0)
NA [1] 
(NA to NA)
[1]
Healthy controls do not have epilepsy.
Seizure type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 16 participants 51 participants
Focal 26 0 26
Generalized 6 0 6
Unclassified (GTCS) 3 0 3
1.Primary Outcome
Title Conners' Continuous Performance Test (CPT) (Double-blind Portion, Primary Variables)
Hide Description

Scores on this test measure attentiveness/vigilance and response time. Primary measures are: D', HRTSD D' represents 'detectability,' and is a derived statistic which measures a participant's ability to distinguish target stimuli from non-target stimuli, and incorporates response time and accuracy factors. The equation for deriving it is proprietary to the test which markets the CPT. A higher, or less negative, score is considered WORSE.

HRTSD represents the standard deviation of participant hit reaction time data, as measured for a variety of different stimuli types across the trial. It is a measure of the participant's ability to maintain attention across the trial. A higher score represents more variability and is considered WORSE.

Time Frame difference in scores on specific variables between MPH 20mg, 10mg, and placebo (randomized to administration at weeks 2, 3, or 4)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Placebo Participants With Epilepsy: Methylphenidate 10 mg Dose Participants With Epilepsy: Methylphenidate 20 mg
Hide Arm/Group Description:

Methylphenidate: Participants received blinded, single-dose capsules during either visit 2, 3, or 4. During one of these visits, they received the placebo capsule.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 10 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 20 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Overall Number of Participants Analyzed 31 31 31
Mean (Standard Deviation)
Unit of Measure: Units
D' -3.3  (0.9) -3.58  (0.78) -3.66  (0.77)
HRTSD 0.19  (0.048) 0.17  (0.034) 0.17  (0.036)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments HRTSD p-value = 0.037; p < 0.05 considered significant
Method ANOVA
Comments Within-subjects contrasts, n=31, df=1
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.055
Comments D' p = 0.055. p < 0.05 considered significant.
Method ANOVA
Comments Within-subjects contrasts, placebo v 10mg v 20mg.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments HRTSD 10mg vs 20mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.758
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments d' 10mg vs 20mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.499
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Symbol-digit Matching Test (Double-blind Portion)
Hide Description Symbol-digit matching test is a measure processing speed and working memory. The task involves matching nonsense symbols with numbers based on a key as quickly as possible within 90s. Score represents the number of correct responses within the time frame. Minimum score is 0. There is not a meaningful 'maximum' score, as there are too many symbols for a participant to successfully complete within the allotted time. A higher score is better.
Time Frame Difference in scores between MPH 20mg, 10mg, or placebo during double-blind portion during which medication was randomized to weeks 2, 3, or 4.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Placebo Participants With Epilepsy: Methylphenidate 10 mg Dose Participants With Epilepsy: Methylphenidate 20 mg
Hide Arm/Group Description:

Methylphenidate: Participants received blinded, single-dose capsules during either visit 2, 3, or 4. During one of these visits, they received the placebo capsule.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 10 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 20 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Overall Number of Participants Analyzed 31 31 31
Mean (Standard Deviation)
Unit of Measure: points
49.8  (11.9) 52.2  (11.6) 50.6  (11.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments SDMT 10mg vs 20mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.071
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Primary Outcome
Title MCG Paragraph Memory Test (Double-blind Portion)
Hide Description MCG paragraph memory test is a measure of verbal memory. Participants are read aloud a long, detailed story, and are then asked to immediately repeat all information they can remember from the story. Each pertinent story element (as pre-defined on a key) is considered 1 correct response. Minimum score is 0, maximum is 100. A higher score is better.
Time Frame Difference in scores between MPH 20mg, 10mg, or placebo, randomized to be given at weeks 2, 3, or 4
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Placebo Participants With Epilepsy: Methylphenidate 10 mg Dose Participants With Epilepsy: Methylphenidate 20 mg
Hide Arm/Group Description:

Methylphenidate: Participants received blinded, single-dose capsules during either visit 2, 3, or 4. During one of these visits, they received the placebo capsule.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 10 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 20 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Overall Number of Participants Analyzed 31 31 31
Mean (Standard Deviation)
Unit of Measure: Points
25.2  (14.8) 27.4  (15.4) 28  (15.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.154
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments MCG 10mg vs 20mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.779
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Primary Outcome
Title Conners CPT Outcomes (Primary Variables) (Open-Label Portion)
Hide Description

Within-groups comparison (between visit 1 and visit 5 within patients with epilepsy, comparing scores at baseline to scores on methylphenidate) as well as a comparison against healthy controls who repeated the cognitive measures an equal number of times (to assess and control for test/retest and placebo improvements).

D' represents 'detectability,' and is a derived statistic which measures a participant's ability to distinguish target stimuli from non-target stimuli, and incorporates response time and accuracy factors. The equation for deriving it is proprietary to the test which markets the CPT. A higher, or less negative, score is considered WORSE.

HRTSD represents the standard deviation of participant hit reaction time data, as measured for a variety of different stimuli types across the trial. It is a measure of the participant's ability to maintain attention across the trial. A higher score represents more variability and is considered WORSE.

Time Frame Difference between scores at baseline (visit 1) and on methylphenidate open-label (visit 5), compared to untreated healthy controls
Hide Outcome Measure Data
Hide Analysis Population Description
PLEASE NOTE: One participant with epilepsy did not record any usable data for Conners CPT due to pressing the wrong key throughout large portions of the trial. Therefore, he is not included in CPT variables (but is included in other analyses).
Arm/Group Title Participants With Epilepsy: Visit 1 (Baseline) Participants With Epilepsy: Visit 5 (Open Label) Healthy Controls: Visit 1 (Baseline) Healthy Controls: Visit 5
Hide Arm/Group Description:
At visit 1, participants underwent neurocognitive batteries and neuropsychiatric questionnaires for baseline assessment. No medications were given at this visit.
Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After four weeks, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Overall Number of Participants Analyzed 27 27 14 14
Mean (Standard Deviation)
Unit of Measure: Units
HRTSD 0.22  (0.04) 0.16  (0.03) 0.20  (0.04) 0.15  (0.03)
D' -2.9  (0.9) -3.8  (0.7) -3.7  (0.5) -4.2  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments Intra-group comparison, HRTSD
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments HRTSD P<0.0001
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Intra-group comparison, HRTSD, healthy controls
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments HRTSD p <0.001 for healthy controls
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Between-group comparisons by 2-way ANOVA, HRTSD
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.322
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments Intra-group comparison, epilepsy, D'
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Intra-group analysis, healthy controls, d'
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Intra-group analysis by 2-way ANOVA, d'
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
5.Primary Outcome
Title Symbol-digit Matching Test (Open Label Phase)
Hide Description Symbol-digit matching test is a measure processing speed and working memory. The task involves matching nonsense symbols with numbers based on a key as quickly as possible within 90s. Score represents the number of correct responses within the time frame. Minimum score is 0. There is not a meaningful 'maximum' score, as there are too many symbols for a participant to successfully complete within the allotted time. A higher score is better.
Time Frame The single-dose double blind phase was followed by an open-label 4-week treatment phase.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Visit 1 (Baseline) Participants With Epilepsy: Visit 5 (Open Label) Healthy Controls: Visit 1 (Baseline) Healthy Controls: Visit 5
Hide Arm/Group Description:
At visit 1, participants underwent neurocognitive batteries and neuropsychiatric questionnaires for baseline assessment. No medications were given at this visit.
Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After four weeks, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Overall Number of Participants Analyzed 28 28 14 14
Mean (Standard Deviation)
Unit of Measure: points
48.1  (11.6) 53.8  (12.0) 55.9  (9.2) 60.1  (8.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Group x time interaction by 2-way ANOVA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.443
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
6.Primary Outcome
Title MCG (Open-label Portion)
Hide Description MCG paragraph memory test is a measure verbal memory. Participants are read aloud a long, detailed story, and are then asked to immediately repeat all information they can remember from the story. Each pertinent story element (as pre-defined on a key) is considered 1 correct response. Minimum score is 0, maximum is 100. A higher score is better.
Time Frame The single-dose double blind phase was followed by an open-label 4-week treatment phase.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Visit 1 (Baseline) Participants With Epilepsy: Visit 5 (Open Label) Healthy Controls: Visit 1 (Baseline) Healthy Controls: Visit 5
Hide Arm/Group Description:
At visit 1, participants underwent neurocognitive batteries and neuropsychiatric questionnaires for baseline assessment. No medications were given at this visit.
Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After four weeks, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Overall Number of Participants Analyzed 28 28 14 14
Mean (Standard Deviation)
Unit of Measure: Points
18.6  (13.4) 30.5  (14.7) 32.7  (16.3) 44.9  (19.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Between-groups analysis by 2-way ANOVA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.906
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
7.Primary Outcome
Title Seizure Frequency (Open-label Portion)
Hide Description Seizures per 28 'at-risk' days. This is a comparison of 28 days prior to baseline visit as compared to seizure rate while taking methylphenidate, adjusted to provide a 'number of seizures per 28 days' measurement.
Time Frame Randomized portion is followed by 1-month open-label portion.
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis only compares the 28 participants who were present in both groups. Participants who participated only in the double-blind portion are represented in that analysis.
Arm/Group Title Participants With Epilepsy (Baseline) Participants With Epilepsy (Open-label Portion)
Hide Arm/Group Description:

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

[Not Specified]
Overall Number of Participants Analyzed 28 28
Mean (Standard Deviation)
Unit of Measure: Seizures per 28 at-risk days
2.8  (6.2) 2.4  (5.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.274
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Primary Outcome
Title QOLIE-89 Aggregate Score
Hide Description

QOLIE-89 is a questionnaire to assess quality of life and subjective cognitive effects. The aggregate score is the overall calculated score. Note: most of its questions are specific to patients with epilepsy, and therefore the questionnaire cannot be validly completed by healthy controls. Therefore, only participants with epilepsy completed the questionnaire.

QOLIE aggregate scores and subscale scores are calculated based on individual patient responses throughout the survey, and according to scoring rules as determined by the creator of the questionnaire. Scores are rated 0 (worst) to 100 (best).

Time Frame Change from baseline to end of methylphenidate open label treatment (end month 2)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy (Baseline) Participants With Epilepsy (Open-label Portion)
Hide Arm/Group Description:

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Note: Because the QOLIE-89 is specific to epilepsy populations, most of its questions are not applicable to healthy controls, and therefore healthy controls did not complete the QOLIE-89.
Overall Number of Participants Analyzed 28 28
Mean (Standard Deviation)
Unit of Measure: Points
60.2  (17.1) 72.0  (16.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
9.Secondary Outcome
Title CPT Scores (Double-blind Portion) (Secondary Variables)
Hide Description

Secondary variables in CPT: hits, omissions, commissions

  • Hits” represents the raw number of accurate responses to target stimuli, out of a maximum of 288. A higher number is better.
  • Omissions” are errors committed when a target stimuli is not appropriately responded to. A higher number is worse. Theoretically, the maximum number of omissions would be 288. A lower number is BETTER.
  • Commissions” are errors committed when a participant responds to a non-target stimuli. Because a participant may make multiple such errors for a given stimuli, there is no raw maximum. A lower number is BETTER.
Time Frame Difference between scores on MPH 20mg, 10mg, or placebo during randomized visits weeks 2, 3, or 4
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Placebo Participants With Epilepsy: Methylphenidate 10 mg Dose Participants With Epilepsy: Methylphenidate 20 mg
Hide Arm/Group Description:

Methylphenidate: Participants received blinded, single-dose capsules during either visit 2, 3, or 4. During one of these visits, they received the placebo capsule.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 10 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 20 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Overall Number of Participants Analyzed 31 31 31
Mean (Standard Deviation)
Unit of Measure: Units
Hits 285.3  (4.5) 286.9  (1.6) 287  (2.7)
Omissions 0.9  (1.5) 0.3  (0.4) 0.3  (0.8)
Commissions 24  (19.9) 21.5  (18.2) 21.2  (15.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments Hits p = 0.04
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments Omissions p = 0.038
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.329
Comments Commissions p = 0.329
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments Hits 10mg vs 20mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.876
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments Omissions 10mg vs 20mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.932
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments Commissions 10mg vs 20mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.898
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
10.Secondary Outcome
Title Seizure Frequency/Severity (Double-blind Portion)
Hide Description Seizures per 28 'at-risk' days. This is a comparison of 28 days prior to baseline visit as compared to seizure rate while taking methylphenidate, adjusted to provide a 'number of seizures per 28 days' measurement.
Time Frame Seizure rate during 28 days prior to study compared to during randomized, single-dose portion, rate adjusted to seizures per 28 patient days.
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants who were present in both groups are included here.
Arm/Group Title Participants With Epilepsy (Baseline) Participants With Epilepsy (Double-blind Portion)
Hide Arm/Group Description:

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

[Not Specified]
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Seizures per 28 at-risk days
2.5  (5.9) 2.0  (5.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Double-blind Portion)
Comments Comparison of baseline rate of seizures (expressed as seizures per 28 days) pre-trial against the rate experienced during the double-blind portion of our trial.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7116
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
11.Secondary Outcome
Title QOLIE-89 Selected Cognitive Subscales (Open-label)
Hide Description

Pre-selected secondary variables were cognitive subscales on the QOLIE-89 felt likely to be affected by MPH: attention/concentration; memory; language; energy/fatigue.

QOLIE aggregate scores and subscale scores are calculated based on individual patient responses throughout the survey, and according to scoring rules as determined by the creator of the questionnaire. Scores are rated 0 (worst) to 100 (best).

Time Frame Comparing baseline (visit 1) to end of open-label (end of week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy (Baseline) Participants With Epilepsy (Open-label Portion)
Hide Arm/Group Description:

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Note: Because the QOLIE-89 is specific to epilepsy populations, most of its questions are not applicable to healthy controls, and therefore healthy controls did not complete the QOLIE-89.
Overall Number of Participants Analyzed 28 28
Mean (Standard Deviation)
Unit of Measure: Points
Attention/Concentration 50.4  (21.4) 74.8  (19.5)
Memory 36.8  (27.0) 59.7  (26.3)
Language 58.1  (27.0) 72.3  (21.9)
Energy/Fatigue 45.9  (21.2) 61.6  (19.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Attention/Concentration subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Memory subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Language subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Energy/fatigue subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
12.Secondary Outcome
Title CPT Outcomes (Secondary Variables) (Open-label Portion)
Hide Description

Omissions, commissions, and hits

  • Hits” represents the raw number of accurate responses to target stimuli, out of a maximum of 288. A higher number is better.
  • Omissions” are errors committed when a target stimuli is not appropriately responded to. A higher number is worse. Theoretically, the maximum number of omissions would be 288. A lower number is BETTER.
  • Commissions” are errors committed when a participant responds to a non-target stimuli. Because a participant may make multiple such errors for a given stimuli, there is no raw maximum. A lower number is BETTER.
Time Frame Baseline (Visit 1) vs end of Open-label (week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
Note: one epilepsy participant's CPT data was invalid/unusable due to pressing the wrong button during the trial.
Arm/Group Title Participants With Epilepsy: Visit 1 (Baseline) Participants With Epilepsy: Visit 5 (Open Label) Healthy Controls: Visit 1 (Baseline) Healthy Controls: Visit 5
Hide Arm/Group Description:
At visit 1, participants underwent neurocognitive batteries and neuropsychiatric questionnaires for baseline assessment. No medications were given at this visit.
Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After four weeks, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Overall Number of Participants Analyzed 27 27 14 14
Mean (Standard Deviation)
Unit of Measure: Points
Hits 284.6  (5.1) 287.6  (0.9) 287  (1.2) 287.6  (0.7)
Omissions 1.0  (1.4) 0.1  (0.3) 0.3  (0.3) 0.1  (0.2)
Commissions 34.8  (18.4) 18.5  (17.8) 16.7  (9.7) 13.2  (16.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments Hits v1 vs v5 epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Hits v1 vs v5 healthy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments 2-way ANOVA epilepsy vs healthy hits
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments Omissions epilepsy v1 vs v5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Omissions v1 vs v5 healthy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Epilepsy v healthy ANOVA Omissions
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments Commissions v1 vs v5 epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Commissions v1 vs v5 healthy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Healthy vs epilepsy ANOVA (2-way) commissions
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
13.Other Pre-specified Outcome
Title Adverse Events Profile (Open-Label)
Hide Description

This is a side-effects reporting scale for anti-epileptic medications. Because it encompasses cognitive and non-cognitive side effects, it was not considered one of our main cognitive/quality of life outcomes of interest. It is used in other studies of AED side effects, however, so was included.

The scale consists of 19 symptoms rated 1 (Never a problem) to 4 (Always or often a problem). Minimum score is 19, maximum score is 76. A higher score is WORSE.

Time Frame Baseline (Visit 1) vs end of Open-label (week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy (Baseline) Participants With Epilepsy (Open-label Portion)
Hide Arm/Group Description:

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Note: Because the questionnaire is specific to epilepsy populations, and the side-effects to AEDs, healthy controls did not complete the QOLIE-89.
Overall Number of Participants Analyzed 28 28
Mean (Standard Deviation)
Unit of Measure: Points
41.9  (8.5) 34.4  (9.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
14.Other Pre-specified Outcome
Title Stimulant Side-effects Checklist
Hide Description

This is a questionnaire covering common stimulant side-effects, intended to help monitor for any significant or common adverse effects.

The scale lists 16 common stimulant side effects rated 0 (absent) to 9 (serious). Minimum score is 0, maximum is 144. A higher score is WORSE.

Time Frame Baseline (Visit 1) vs end of Open-label (week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy (Baseline) Participants With Epilepsy (Open-label Portion)
Hide Arm/Group Description:

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Note: Because the SSC is specific to medication side effects, healthy controls did not complete the questionnaire.
Overall Number of Participants Analyzed 28 28
Mean (Standard Deviation)
Unit of Measure: Points
37.2  (21.0) 27.3  (23.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Note: Stimulant side-effect score *decreased* with addition of open-label stimulant.
Method t-test, 2 sided
Comments [Not Specified]
15.Other Pre-specified Outcome
Title Neuropsychiatric Questionnaires
Hide Description

Beck Depression Inventory, Beck Anxiety Inventory, Apathy Evaluation Scale. These were not primary or secondary variables of interest given methylphenidate's primary expected action being on cognition. Included given one author's interest, as other studies suggesting psychiatric improvements (particularly apathy and depression) with methylphenidate.

BDI is a common clinical and research measure of depression. It has 21 questions and is scored 0 (no depression) to 63 (most severe depression). A higher score is worse.

BAI is a measure of anxiety, which also has 21 questions and is scored 0 (no anxiety) to 63 (most severe anxiety). A higher score is worse.

AES is a measure of clinical apathy, and is an 18-item scale. It rates symptoms as "not at all," "slightly," "somewhat," or "a lot," which are then converted to numerical values 1 (least apathy) to 4 (most apathy). Scores range from 18 (no apathy) to 72 (most apathy).

Time Frame Baseline (Visit 1) vs end of Open-label (week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Visit 1 (Baseline) Participants With Epilepsy: Visit 5 (Open Label) Healthy Controls: Visit 1 (Baseline) Healthy Controls: Visit 5
Hide Arm/Group Description:
At visit 1, participants underwent neurocognitive batteries and neuropsychiatric questionnaires for baseline assessment. No medications were given at this visit.
Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After four weeks, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Overall Number of Participants Analyzed 28 28 14 14
Mean (Standard Deviation)
Unit of Measure: Points
BDI 9.6  (7.3) 6.4  (6.1) 2.0  (1.7) 1.1  (1.5)
BAI 10.9  (11.1) 9.6  (9.2) 2.4  (5.1) 1.7  (2.1)
AES 31.2  (5.6) 28.7  (7.0) 23.3  (5.0) 22.9  (4.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments BDI epilepsy v1 vs v5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Healthy controls BDI v1 vs v5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Between-group comparison 2-way ANOVA BDI
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.191
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments BAI visit 1 vs visit 5 epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments BAI visit 1 vs visit 5 healthy controls
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.477
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Between-groups comparison 2-way ANOVA BAI
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.792
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments AES visit 1 vs visit 5 epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments AES visit 1 vs visit 5 healthy controls
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.646
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Between-groups comparison 2-way ANOVA AES
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.222
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
16.Post-Hoc Outcome
Title QOLIE-89 Additional Subscales (Open-label)
Hide Description

These are the remaining subscales of the QOLIE-89. These were not pre-specified variables of interest or intentional post-hoc analyses, but are automatically calculated in scoring the QOLIE-89 and are included ONLY for completeness of data submission.

QOLIE aggregate scores and subscale scores are calculated based on individual patient responses throughout the survey, and according to scoring rules as determined by the creator of the questionnaire. Scores are rated 0 (worst) to 100 (best).

Time Frame Visit 1 (baseline) vs end of open-label (week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy (Baseline) Participants With Epilepsy (Open-label Portion)
Hide Arm/Group Description:

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Note: Because the QOLIE-89 is specific to epilepsy populations, most of its questions are not applicable to healthy controls, and therefore healthy controls did not complete the QOLIE-89.
Overall Number of Participants Analyzed 28 28
Mean (Standard Deviation)
Unit of Measure: Points
Health Perceptions 55.2  (21.4) 63.4  (22.4)
Overall QOL (pt rating) 65.5  (18.4) 73.0  (14.3)
Physical Function 78.0  (27.4) 83.2  (22.4)
Role Limitations (Emotional) 67.8  (43.0) 79.3  (30.0)
Role Limitations (Physical) 62.8  (36.4) 82.8  (30.6)
Pain 70.4  (30.9) 78.1  (22.8)
Work/Driving/Social 61.1  (27.0) 69.5  (22.4)
Emotional Wellbeing 70.3  (17.0) 75.1  (17.8)
Health Discouragement 66.4  (30.8) 81.8  (21.3)
Seizure Worry 55.5  (28.9) 61.9  (31.7)
Medication Effects 48.1  (28.7) 50.9  (30.9)
Social Support 71.2  (23.4) 73.0  (24.5)
Social Isolation 74.6  (27.6) 81.4  (21.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Health Perceptions
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Overall QOL (subjectively rated by participants on the scale)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Physical Function
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Role Limitations (Emotional)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Role Limitations (Physical)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Pain
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Work/Driving/Social
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Emotional Wellbeing
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.077
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Health Discouragement
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Seizure Worry
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Medication Effects
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.609
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Social Support
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.626
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy (Baseline), Participants With Epilepsy (Open-label Portion)
Comments Social Isolation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.103
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
17.Post-Hoc Outcome
Title Remaining CPT Variables (Open-label)
Hide Description

These are automatically-calculated CPT variables which were not pre-specified variables of interest or intentional post-hoc analyses. They are included ONLY for completeness of data. They include hit reaction time (HRT), variability (VAR), and perseverations (PRS).

Hit reaction time represents to the average number of milliseconds required for a participant to respond to target stimuli. There are no meaningful absolute minimum or maximum scores, though 101ms is the current fastest verified response time per our review. A higher score is WORSE.

Variability refers to variations in response time across individual blocks of time within the trial. It differs from HRTSD in that HRTSD measures variability across the entire trial. Minimum is 0. There are no absolute maximums. A higher score is WORSE.

Perseverations are errors made either faster than physiologically possible (<100ms). Minimum is 0, there is no maximum. Higher scores are WORSE.

Time Frame Baseline vs end of open-label (week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
Note: One participant's CPT data was invalid
Arm/Group Title Participants With Epilepsy: Visit 1 (Baseline) Participants With Epilepsy: Visit 5 (Open Label) Healthy Controls: Visit 1 (Baseline) Healthy Controls: Visit 5
Hide Arm/Group Description:
At visit 1, participants underwent neurocognitive batteries and neuropsychiatric questionnaires for baseline assessment. No medications were given at this visit.
Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After four weeks, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Overall Number of Participants Analyzed 27 27 14 14
Mean (Standard Deviation)
Unit of Measure: Units
Variability (units) 0.05  (0.02) 0.04  (0.008) 0.042  (0.01) 0.035  (0.009)
Perseverations (units) 0.2  (0.5) 0.01  (0.05) 0.08  (0.2) 0.0  (0.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments Variability v1 vs v5 epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Variability v1 vs v5 healthy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.096
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Variability 2-way ANOVA healthy vs epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.136
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments Perseverations v1 vs v5 epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Perseverations v1 vs v5 healthy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.104
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments Perseverations 2-way ANOVA healthy vs epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.661
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
18.Post-Hoc Outcome
Title Remaining CPT Variables (Double-blind Portion)
Hide Description

Remaining CPT variables are automatically calculated by the program. They were not pre-specified variables of interest nor intentional post-hoc analyses. They are included ONLY for completeness of data submission.

Hit reaction time represents to the average number of milliseconds required for a participant to respond to target stimuli. There are no meaningful absolute minimum or maximum scores, though 101ms is the current fastest verified response time per our review. A higher score is WORSE.

Variability refers to variations in response time across individual blocks of time within the trial. It differs from HRTSD in that HRTSD measures variability across the entire trial. Minimum is 0. There are no absolute maximums. A higher score is WORSE.

Perseverations are errors made either faster than physiologically possible (<100ms). Minimum is 0, there is no maximum. Higher scores are WORSE.

Time Frame Placebo vs 10mg vs 20mg (visits 2, 3, 4)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Placebo Participants With Epilepsy: Methylphenidate 10 mg Dose Participants With Epilepsy: Methylphenidate 20 mg
Hide Arm/Group Description:

Methylphenidate: Participants received blinded, single-dose capsules during either visit 2, 3, or 4. During one of these visits, they received the placebo capsule.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 10 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 20 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Overall Number of Participants Analyzed 31 31 31
Mean (Standard Deviation)
Unit of Measure: Units
Variability (units) 0.04  (0.02) 0.04  (0.01) 0.04  (0.01)
Perseverations (units) 0.06  (0.2) 0.05  (0.2) 0.04  (0.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments Variability ANOVA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.397
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments Perseverations ANOVA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.745
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments 10mg vs 20mg variability
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.362
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments 10mg vs 20mg perseverations
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.745
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
19.Post-Hoc Outcome
Title Hit Reaction Time (Double Blind)
Hide Description

Hit reaction time represents the average number of milliseconds required for a participant to respond to target stimuli. There are no meaningful absolute minimum or maximum scores, though 101ms is the current fastest verified response time per our review. A higher score is WORSE.

This was not a pre-specified variable or an intentional post-hoc analysis, but it is calculated automatically and included here only for completeness of data submission.

Time Frame Visits 2 vs 3 vs 4 on randomized medication doses.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Placebo Participants With Epilepsy: Methylphenidate 10 mg Dose Participants With Epilepsy: Methylphenidate 20 mg
Hide Arm/Group Description:

Methylphenidate: Participants received blinded, single-dose capsules during either visit 2, 3, or 4. During one of these visits, they received the placebo capsule.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 10 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Participants received blinded, single-dose capsules of during visits 2, 3, and 4. During one of these visits, they received the methylphenidate 20 mg dose.

At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Overall Number of Participants Analyzed 31 31 31
Mean (Standard Deviation)
Unit of Measure: ms
437.4  (68.9) 433.9  (65.2) 435.6  (68.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Placebo, Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments HRT ANOVA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Methylphenidate 10 mg Dose, Participants With Epilepsy: Methylphenidate 20 mg
Comments HRT 10mg vs 20mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.793
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
20.Post-Hoc Outcome
Title Hit Reaction Time (Open-Label)
Hide Description

Hit reaction time represents the average number of milliseconds required for a participant to respond to target stimuli. There are no meaningful absolute minimum or maximum scores, though 101ms is the current fastest verified response time per our review. A higher score is WORSE.

This was not a pre-specified variable or an intentional post-hoc analysis, but it is calculated automatically and included here only for completeness of data submission.

Time Frame Visits 2 vs 3 vs 4 on randomized medication doses.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With Epilepsy: Visit 1 (Baseline) Participants With Epilepsy: Visit 5 (Open Label) Healthy Controls: Visit 1 (Baseline) Healthy Controls: Visit 5
Hide Arm/Group Description:
At visit 1, participants underwent neurocognitive batteries and neuropsychiatric questionnaires for baseline assessment. No medications were given at this visit.
Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After four weeks, their scores on the batteries and questionnaires were again assessed.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Overall Number of Participants Analyzed 28 28 14 14
Mean (Standard Deviation)
Unit of Measure: Milliseconds
431.2  (69.4) 425.7  (60.2) 447.7  (62.2) 423.4  (63.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label)
Comments HRT v1 vs v5 epilepsy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments HRT v1 vs v5 healthy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Participants With Epilepsy: Visit 1 (Baseline), Participants With Epilepsy: Visit 5 (Open Label), Healthy Controls: Visit 1 (Baseline), Healthy Controls: Visit 5
Comments HRT epilepsy vs healthy ANOVA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Time Frame During entirety of pt participation (~2 months), throughout entirety of study.
Adverse Event Reporting Description Commonly-expected side effects (anxiety, tachycardia) were routinely asked about at the end of participant visits, and responses recorded. Vital signs were checked at visits 1, 4, and 5. Fatigue was reported spontaneously by the affected participant and was not assessed routinely.
 
Arm/Group Title Participants With Epilepsy (Open-label) Placebo, 20mg, Then 10mg (Double-blind) Placebo, 10mg, Then 20mg (Double-blind) 10mg, 20mg, Then Placebo (Double-blind) 10mg, Placebo, Then 20mg (Double-blind) 20mg, 10mg, Then Placebo (Double-blind) 20mg, Placebo, Then 10mg (Double-blind) 40mg, 20mg, Then Placebo (One Participant) Healthy Controls
Hide Arm/Group Description Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After a four week treatment trial, their scores on the batteries and questionnaires were again assessed.

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules in the following order:

Placebo, 20mg of methylphenidate, 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules in the following order:

Placebo, 10mg of methylphenidate, 20mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules in the following order:

10mg of methylphenidate, 20mg of methylphenidate, Placebo.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules in the following order:

10mg of methylphenidate, Placebo, 20mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules in the following order:

20mg of methylphenidate, 10mg of methylphenidate, Placebo.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules in the following order:

20mg of methylphenidate, Placebo, 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

This study was originally intended to use 40mg, 20mg, and placebo doses rather than 20mg, 10mg, and placebo. This individual developed tachycardia (see adverse events) on the 40mg dose, and was withdrawn from the double-blind portion as a result. We removed the 40mg doses from this study and replaced them with 10mg doses. No other participant received a 40mg dose. This participant rejoined the open-label portion after consultation with his PCP due to significant perceived benefit from the MPH dose. Healthy controls will complete the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but will not be exposed to study medication. They are included as a control group for the open-label phase of the study (visit 1 vs visit 5) only.
All-Cause Mortality
Participants With Epilepsy (Open-label) Placebo, 20mg, Then 10mg (Double-blind) Placebo, 10mg, Then 20mg (Double-blind) 10mg, 20mg, Then Placebo (Double-blind) 10mg, Placebo, Then 20mg (Double-blind) 20mg, 10mg, Then Placebo (Double-blind) 20mg, Placebo, Then 10mg (Double-blind) 40mg, 20mg, Then Placebo (One Participant) Healthy Controls
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Participants With Epilepsy (Open-label) Placebo, 20mg, Then 10mg (Double-blind) Placebo, 10mg, Then 20mg (Double-blind) 10mg, 20mg, Then Placebo (Double-blind) 10mg, Placebo, Then 20mg (Double-blind) 20mg, 10mg, Then Placebo (Double-blind) 20mg, Placebo, Then 10mg (Double-blind) 40mg, 20mg, Then Placebo (One Participant) Healthy Controls
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/30 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/5 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/5 (0.00%)      0/1 (0.00%)      0/15 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Participants With Epilepsy (Open-label) Placebo, 20mg, Then 10mg (Double-blind) Placebo, 10mg, Then 20mg (Double-blind) 10mg, 20mg, Then Placebo (Double-blind) 10mg, Placebo, Then 20mg (Double-blind) 20mg, 10mg, Then Placebo (Double-blind) 20mg, Placebo, Then 10mg (Double-blind) 40mg, 20mg, Then Placebo (One Participant) Healthy Controls
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/30 (6.67%)      0/6 (0.00%)      1/6 (16.67%)      0/5 (0.00%)      1/6 (16.67%)      2/6 (33.33%)      0/5 (0.00%)      1/1 (100.00%)      0/15 (0.00%)    
Cardiac disorders                   
Tachycardia  [1]  0/30 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/5 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/5 (0.00%)  0 1/1 (100.00%)  1 0/15 (0.00%)  0
General disorders                   
Fatigue * [2]  1/30 (3.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/5 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/5 (0.00%)  0 0/1 (0.00%)  0 0/15 (0.00%)  0
Psychiatric disorders                   
Anxiety/panic attack  [3]  0/30 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/5 (0.00%)  0 1/6 (16.67%)  1 2/6 (33.33%)  2 0/5 (0.00%)  0 0/1 (0.00%)  0 0/15 (0.00%)  0
Increased anxiety  [4]  1/30 (3.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/5 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/5 (0.00%)  0 0/1 (0.00%)  0 0/15 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
~4 hours after dose had 2-3 hours of HR ~160bpm w/ no other symptoms. Resolved w/ no intervention. No other symptoms. BP stable per pt report. Pt did not seek care. We withdrew pt.
[2]
One participant tolerated all three randomized doses, yet experienced fatigue on the open-label dose. This participant elected to withdraw from the open-label trial.
[3]
Four participants experienced a period of anxiety following ingestion of medication, lasting 1-3 hours, without other symptoms. Vitals were stable, and symptoms resolved on their own. Two of the four elected to withdraw.
[4]
One participant reported increased anxiety after having tolerated all of the blinded capsules in the randomized portion. This participant elected to withdraw from the open- label portion.
Relatively small sample; Control is healthy patients rather than epilepsy patients; Healthy controls improve more on re-testing than epilepsy patients; Single-dose portion does not mirror clinical practice; open-label portion is not blinded.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jesse Adams, MD
Organization: Stanford University
Phone: 2069144771
EMail: jadamsuw@stanford.edu
Layout table for additonal information
Responsible Party: Kimford Jay Meador, Stanford University
ClinicalTrials.gov Identifier: NCT02178995     History of Changes
Other Study ID Numbers: MPH in epilepsy
First Submitted: June 24, 2014
First Posted: July 1, 2014
Results First Submitted: June 4, 2016
Results First Posted: August 31, 2016
Last Update Posted: May 30, 2017