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Comparison of Keppra and Clonidine in the Treatment of Tics

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ClinicalTrials.gov Identifier: NCT00370838
Recruitment Status : Completed
First Posted : September 1, 2006
Results First Posted : September 7, 2011
Last Update Posted : September 7, 2011
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Harvey S. Singer, Johns Hopkins University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Tic Disorders
Tourette Syndrome
Interventions Drug: Levetiracetam
Drug: Clonidine
Enrollment 12
Recruitment Details  
Pre-assignment Details 12 participants signed informed consent, but 2 participants were never randomized to treatment arm.
Arm/Group Title First Levetiracetam Then Clonidine Clonidine First, Then Levetiracetam
Hide Arm/Group Description

Participants first received levetiracetam: starting dose of 10 milligram/killigram/day, increased weekly by 5-10 milligram/killigram/day, to a maximum of 50 milligram/killigram/day (25 milligram/killigram twice a day; 2,500 mg per day).

In the second period, participants received clonidine (days 65-107), packaged in look-alike capsules: starting dose was 0.05 milligrams twice a day, if needed, the dose increased weekly by 0.05-0.1 milligrams. The maximum dose was 0.4 milligrams (0.2 milligrams twice a day).

Wash out phase: Between the two treatment phases, medication tapered over a ten day period: levetiracetam by 5-10 mg/kg/day every third day; clonidine by 0.05 - 0.1 mg every third day. Subjects were off medication for 5 days before starting the second phase of the cross over study.

Taper: After the two treatment phases, medication tapered over a ten day period as in Wash-out phase (see above).

Participants first received clonidine, packaged in look-alike capsules: starting dose was 0.05 milligram (mg) twice a day, if needed, the dose increased weekly by 0.05-0.1 mg. The maximum dose was 0.4 mg (0.2 mg twice a day (BID)).

In the second period, participants received levetiracetam: starting dose of 10 mg/killigram(kg)/day, increased weekly by 5-10 mg/kg/day, to a maximum of 50 mg/kg/day (25 mg/kg BID; 2,500 mg per day).

Wash out phase: Between the two treatment phases, medication tapered over a ten day period: levetiracetam by 5-10 mg/kg/day every third day; clonidine by 0.05 - 0.1 mg every third day. Subjects were off medication for 5 days before starting the second phase of the cross over study.

Taper: After the two treatment phases, medication tapered over a ten day period as in Wash-out phase (see above).

Period Title: Period 1 (Days 8-50)
Started 7 3
Completed 7 3
Not Completed 0 0
Period Title: Washout (Days 51-64)
Started 7 3
Completed 7 3
Not Completed 0 0
Period Title: Period 2 (Days 65-107)
Started 7 3
Completed 7 3
Not Completed 0 0
Period Title: Taper
Started 7 3
Completed 7 3
Not Completed 0 0
Arm/Group Title Levetiracetam First, Then Clonidine Clonidine First, Then Levetiracetam Total
Hide Arm/Group Description

Participants first received levetiracetam: starting dose of 10 milligram/killigram/day, increased weekly by 5-10 milligram/killigram/day, to a maximum of 50 milligram/killigram/day (25 milligram/killigram twice a day; 2,500 mg per day).

In the second period, participants received clonidine (days 65-107), packaged in look-alike capsules: starting dose was 0.05 milligrams twice a day, if needed, the dose increased weekly by 0.05-0.1 milligrams. The maximum dose was 0.4 milligrams (0.2 milligrams twice a day).

Wash out phase: Between the two treatment phases, medication tapered over a ten day period: levetiracetam by 5-10 mg/kg/day every third day; clonidine by 0.05 - 0.1 mg every third day. Subjects were off medication for 5 days before starting the second phase of the cross over study.

Taper: After the two treatment phases, medication tapered over a ten day period as in Wash-out phase (see above).

Participants first received clonidine, packaged in look-alike capsules: starting dose was 0.05 milligram (mg) twice a day, if needed, the dose increased weekly by 0.05-0.1 mg. The maximum dose was 0.4 mg (0.2 mg twice a day (BID)).

In the second period, participants received levetiracetam: starting dose of 10 mg/killigram(kg)/day, increased weekly by 5-10 mg/kg/day, to a maximum of 50 mg/kg/day (25 mg/kg BID; 2,500 mg per day).

Wash out phase: Between the two treatment phases, medication tapered over a ten day period: levetiracetam by 5-10 mg/kg/day every third day; clonidine by 0.05 - 0.1 mg every third day. Subjects were off medication for 5 days before starting the second phase of the cross over study.

Taper: After the two treatment phases, medication tapered over a ten day period as in Wash-out phase (see above).

Total of all reporting groups
Overall Number of Baseline Participants 7 3 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 3 participants 10 participants
<=18 years
6
  85.7%
2
  66.7%
8
  80.0%
Between 18 and 65 years
1
  14.3%
1
  33.3%
2
  20.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 3 participants 10 participants
14.5  (6.4) 16.0  (4.4) 14.9  (5.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 3 participants 10 participants
Female
1
  14.3%
2
  66.7%
3
  30.0%
Male
6
  85.7%
1
  33.3%
7
  70.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 7 participants 3 participants 10 participants
7 3 10
1.Primary Outcome
Title Yale Global Tic Severity Scale (YGTSS):
Hide Description The YGTSS is a semi-structured clinical interview designed to measure current tic severity [Leckman et al., 1989], and consists of separate rating of motor (0-25) and vocal (0-25) tics. Ratings are made along 5 discriminant dimensions, scaled 0-5 for each including number, frequency, intensity, complexity, and interference. Total of these scores (0-50) is a Total Tic Score (TTS). The YGTSS contains an impairment ranking, 0-50 points, based on the impact of the tic disorder on areas such as self esteem, family life, social acceptance, and school. 0=no tics present; 100=most severe tics.
Time Frame Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Clonidine
Hide Arm/Group Description:
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 45.2  (12.7) 48.7  (9.6)
Final 48.8  (21.8) 43.1  (11.2)
2.Primary Outcome
Title Total Tic Score
Hide Description The TTS is a portion of the YGTSS [Leckman et al., 1989], and consists of separate rating of motor (0-25) and vocal (0-25) tics. Ratings are made along 5 discriminant dimensions, scaled 0-5 for each including number, frequency, intensity, complexity, and interference. Total of these scores (0-50) is a Total Tic Score (TTS). A score of 0 represent no tics present, a score of 50 represents the most severe tics in each category listed.
Time Frame Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Clonidine
Hide Arm/Group Description:
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 22.7  (5.7) 25.2  (4.3)
Final 23.6  (10.6) 21.8  (4.4)
3.Secondary Outcome
Title Clinical Global Impression-Improvement (CGI-I):
Hide Description Clinical Global Impression-Improvement (CGI-I): The CGI-I is used to compare current severity to baseline. A score of 1 corresponds to "very much improved; 2 equals "much improved;" 3 denotes minimal change; and 4 represents "no change." Scores above 4 are used to indicate deterioration, i.e., 5 equals "minimally worse;" 6 is "much worse;" and 7 is "very much worse."
Time Frame Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Clonidine
Hide Arm/Group Description:
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 4.1  (0.74) 4.1  (0.6)
Final 4.1  (0.74) 4  (0.5)
4.Secondary Outcome
Title Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS):
Hide Description The severity of obsessive-compulsive disorder (OCD) is evaluated using the CY-BOCS [Scahill et al 1997]. Obsessions and compulsions are rated on 5 separate scales yielding three summary scores: Obsessions (0-20), Compulsions (0-20) and Total score (0-40). The CY-BOCS is the most widely used instrument to assess the severity of OCD symptoms in research studies. It includes checklist of specific obsessions and compulsions followed by examiner ratings of time spent, interference, distress, resistance and control over the obsessions and compulsions.0=no obsessions or compulsions; 40=most severe OC
Time Frame Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Clonidine
Hide Arm/Group Description:
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 4.7  (5) 3.1  (4.1)
Final 2.2  (3.7) 3.2  (4.5)
5.Secondary Outcome
Title DuPaul Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale:
Hide Description The presence of Attention Deficit Hyperactivity Disorder (ADHD) symptoms are assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) version of the DuPaul ADHD rating scale, which incorporates the symptom items for ADHD from the DSM into a rating scale format that quantifies symptom severity. Each item is rated as not at all, just a little, pretty much, and very much (0, 1, 2, and 3). There are 18 items in total are summed, with a minimum score of 0 (meaning no inattention or hyperactivity) with a maximum score of 54 (severe inattention and hyperactivity).
Time Frame Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Clonidine
Hide Arm/Group Description:
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 12.5  (10.3) 12.6  (11.1)
Final 12.7  (10.6) 11.9  (10.6)
6.Secondary Outcome
Title Multidimensional Anxiety Scale for Children (MASC):
Hide Description The child's anxiety will be followed using the multidimensional Anxiety Scale for Children (MASC) (Stallings and March, 1995) and is now considered the preferred instrument for rating childhood anxiety. It is a 39-item questionnaire, ranking each item as "Never", "Rarely", "Sometimes", or "Often" (0, 1, 2, 3). The sum of all responses yeilds a score (maximum MASC score is 117). A score of 0 represents no anxiety, and a score of 117 represents severe anxiety.
Time Frame Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Clonidine
Hide Arm/Group Description:
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 32.9  (15.4) 25.2  (17.1)
Final 27.5  (16.2) 25  (14.7)
7.Secondary Outcome
Title Modified Pittsburgh Side Effect Scale
Hide Description Side effects will be assessed by an expanded (modified) Pittsburgh Side Effect Scale modified to include side effects of levetiracetam and clonidine. Significant adverse events will be reported to the UCB, JCCI, and FDA within 24 hours. Positive responses are tallied as "number of side effects" for the responding period.
Time Frame Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Clonidine
Hide Arm/Group Description:
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Number of Side Effects
2.1  (2.1) 3.4  (4.5)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Levetiracetam Clonidine
Hide Arm/Group Description Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase. Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
All-Cause Mortality
Levetiracetam Clonidine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Levetiracetam Clonidine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Levetiracetam Clonidine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      10/10 (100.00%)    
General disorders     
Irritability *  3/10 (30.00%)  7 2/10 (20.00%)  2
Sad/depressed *  2/10 (20.00%)  4 1/10 (10.00%)  1
Hyperactive *  2/10 (20.00%)  2 0/10 (0.00%)  0
Tired/sleepy *  2/10 (20.00%)  2 5/10 (50.00%)  17
Anxious *  3/10 (30.00%)  3 4/10 (40.00%)  4
Lethargic *  1/10 (10.00%)  1 2/10 (20.00%)  2
Fatigue *  1/10 (10.00%)  2 3/10 (30.00%)  3
Dizzy *  1/10 (10.00%)  1 1/10 (10.00%)  2
Stomache ache *  0/10 (0.00%)  0 2/10 (20.00%)  2
Dry mouth *  1/10 (10.00%)  1 1/10 (10.00%)  1
Insomnia *  2/10 (20.00%)  2 2/10 (20.00%)  5
Loss of appetite *  1/10 (10.00%)  1 0/10 (0.00%)  0
Sleepwalking *  0/10 (0.00%)  0 1/10 (10.00%)  1
Psychiatric disorders     
Aggression *  2/10 (20.00%)  5 3/10 (30.00%)  3
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Harvey Singer
Organization: Johns Hopkins University
Phone: 410-955-7212
EMail: hsinger@jhmi.edu
Layout table for additonal information
Responsible Party: Harvey S. Singer, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00370838     History of Changes
Other Study ID Numbers: TSkepclon
First Submitted: August 30, 2006
First Posted: September 1, 2006
Results First Submitted: June 22, 2011
Results First Posted: September 7, 2011
Last Update Posted: September 7, 2011