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Trial record 48 of 135 for:    AMITRIPTYLINE

The Childhood and Adolescent Migraine Prevention Study (CHAMP)

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: NCT01581281
Recruitment Status : Terminated (Interim assessment provided sufficient data to answer study questions)
First Posted : April 20, 2012
Results First Posted : August 10, 2017
Last Update Posted : August 10, 2017
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Migraine
Migraine Disorders
Headache
Interventions Drug: Amitriptyline
Drug: Topiramate
Drug: Placebo
Enrollment 488
Recruitment Details From July 16, 2012 through November 24, 2014, 488 patients were assessed for eligibility from 31 sites in the United States. Of those, 361 patients underwent randomization.
Pre-assignment Details Of the patients assessed for eligibility, 21 (4%) did not undergo randomization owing to early trial closure and 106 (22%) were excluded. Eighty-one (81) were excluded due to not meeting inclusion criteria, 25 declined participation (13 were unwilling, but eligibility was otherwise confirmed and 12 were willing and eligibility was unknown).
Arm/Group Title Topiramate Placebo Amitriptyline
Hide Arm/Group Description Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved. Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms). Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Period Title: Overall Study
Started 145 72 144
Completed 130 66 132
Not Completed 15 6 12
Reason Not Completed
Early Study Closure             15             6             12
Arm/Group Title Topiramate Placebo Amitriptyline Total
Hide Arm/Group Description Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved. Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms). Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved. Total of all reporting groups
Overall Number of Baseline Participants 145 72 144 361
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 72 participants 144 participants 361 participants
<=18 years
145
 100.0%
72
 100.0%
144
 100.0%
361
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 145 participants 72 participants 144 participants 361 participants
14.2  (2.5) 14.2  (2.2) 14.2  (2.4) 14.2  (2.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 72 participants 144 participants 361 participants
Female
101
  69.7%
49
  68.1%
97
  67.4%
247
  68.4%
Male
44
  30.3%
23
  31.9%
47
  32.6%
114
  31.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 72 participants 144 participants 361 participants
Hispanic or Latino
14
   9.7%
6
   8.3%
8
   5.6%
28
   7.8%
Not Hispanic or Latino
123
  84.8%
65
  90.3%
128
  88.9%
316
  87.5%
Unknown or Not Reported
8
   5.5%
1
   1.4%
8
   5.6%
17
   4.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 72 participants 144 participants 361 participants
American Indian or Alaska Native
14
   9.7%
5
   6.9%
8
   5.6%
27
   7.5%
Asian
6
   4.1%
0
   0.0%
0
   0.0%
6
   1.7%
Native Hawaiian or Other Pacific Islander
1
   0.7%
0
   0.0%
0
   0.0%
1
   0.3%
Black or African American
24
  16.6%
17
  23.6%
26
  18.1%
67
  18.6%
White
98
  67.6%
48
  66.7%
107
  74.3%
253
  70.1%
More than one race NA [1]  NA [1]  NA [1]  NA [2] 
Unknown or Not Reported
2
   1.4%
2
   2.8%
3
   2.1%
7
   1.9%
[1]
data not collected
[2]
Total not calculated because data are not available (NA) in one or more arms.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 145 participants 72 participants 144 participants 361 participants
145
 100.0%
72
 100.0%
144
 100.0%
361
 100.0%
Headache Days   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 145 participants 72 participants 144 participants 361 participants
11.5  (6.1) 11.0  (6.3) 11.5  (6.2) 11.4  (6.1)
[1]
Measure Description: Number of headache days during 28-day baseline period
Pediatric Migriane Disability Assessment Score (PedMIDAS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 145 participants 72 participants 144 participants 361 participants
42.6  (27.4) 42.9  (26.7) 40.6  (26.4) 41.9  (26.8)
[1]
Measure Description: Scores on the PedMIDAS range from 0 to 240, with a score of 1 to 10 indicating no disability, 11 to 30 indicating mild disability, 31 to 50 indicating moderate disability, and more than 50 indicating severe disability.
1.Primary Outcome
Title Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days
Hide Description

The primary endpoint was a ≥ 50% reduction in headache frequency from the 28 days (4 weeks) baseline period prior to randomization to the last 28 days (4 weeks) of the trial. Headache frequency was defined as the number of days with headache for a given four week 28 day (4 week) period. A headache day was defined as any day during which any headache occurs within a 24 hour period, starting and ending at midnight.

For each participant, the primary endpoint involved a determination of whether a 50% or greater reduction in headache frequency was observed during the last 4 weeks of active treatment as compared with the headache frequency during the 4-week baseline period. Results were compared across the three treatment groups.

Time Frame 4 week baseline period and last 4 weeks of the 24-week trial
Hide Outcome Measure Data
Hide Analysis Population Description
The primary endpoint involved a determination of whether a 50% or greater reduction in headache frequency was observed during the last 4 weeks of active treatment as compared with the headache frequency during the 4-week baseline period between the participants receiving amitriptyline and participants receiving placebo.
Arm/Group Title Topiramate Placebo Amitriptyline
Hide Arm/Group Description:
Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved
Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms).
Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Overall Number of Participants Analyzed 130 66 132
Measure Type: Count of Participants
Unit of Measure: Participants
72
  55.4%
40
  60.6%
69
  52.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Amitriptyline
Comments Logistic regression models were used to estimate the odds of successful primary endpoint for amitriptyline relative to placebo. The analyses followed the intention to treat principle, imputing an outcome of “failure” for any participant who withdrew early for any reason or did not provide week 24 headache diary data (endpoint data). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2636
Comments A Bonferroni approach was used to control the type I error rate. Because there were three comparisons, the Bonferroni corrected level of significance is 0.017 (= 0.05 / 3).
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.71
Confidence Interval (2-Sided) 98.3%
0.34 to 1.48
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Topiramate, Placebo
Comments Logistic regression models were used to estimate the odds of successful primary endpoint for topiramate relative to placebo. The analyses followed the intention to treat principle, imputing an outcome of “failure” for any participant who withdrew early for any reason or did not provide week 24 headache diary data (endpoint data). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4821
Comments A Bonferroni approach was used to control the type I error rate. Because there were three comparisons of interest, the Bonferroni corrected level of significance is 0.017 ( = 0.05 / 3).
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.81
Confidence Interval (2-Sided) 98.3%
0.39 to 1.68
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Topiramate, Amitriptyline
Comments Logistic regression models were used to estimate the odds of successful primary endpoint for topiramate relative to amitriptyline. The analyses followed the intention to treat principle, imputing an outcome of “failure” for any participant who withdrew early for any reason or did not provide week 24 headache diary data (endpoint data). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6107
Comments A Bonferroni approach was used to control the type I error rate. Because there were three comparisons of interest, the Bonferroni corrected level of significance is 0.017 ( = 0.05 / 3).
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.88
Confidence Interval (2-Sided) 98.3%
0.49 to 1.59
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Absolute Headache Disability Score on PedMIDAS
Hide Description

The PedMIDAS scale which evaluated the impact of headaches in school, home, play, and social activities, is comprised of six items that pertain to days missed in various activities over the past 90 days. Questions were answered by the youth in consultation with their parents and reviewed by study staff. The PedMIDAS scale was administered at baseline (covering the three months prior to enrollment) and at the 24-week endpoint visit (the end of the maintenance period, covering three months of enrollment). A total PedMIDAS score (sum of items 1-6) was used in this trial. Scores range from 0-240; with a score of 0-10 indicating no disability, 11-30 mild disability, 31-50 moderate disability, and more than 50 severe disability in daily activities. The main outcome measure for this comparison will be the difference in the baseline and endpoint (24 week) PedMIDAS total scores for:

  1. Amitriptyline vs. Placebo
  2. Topiramate vs. Placebo
  3. Amitriptyline vs Topiramate
Time Frame baseline and 24 week endpoint
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Topiramate Placebo Amitriptyline
Hide Arm/Group Description:
Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms).
Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Overall Number of Participants Analyzed 130 66 132
Mean (Standard Deviation)
Unit of Measure: units on a scale
-26.8  (27.5) -22.6  (29.42) -22.5  (26.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Amitriptyline
Comments The mean change from baseline in PedMIDAS score over time for the three groups was assessed using a linear regression model for each of the three pairwise comparisons (Amitriptyline relative to placebo, Topiramate relative to placebo, and Amitriptyline relative to Topiramate), adjusted for the baseline PedMIDAS score. The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9137
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-6.64 to 5.95
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Topiramate, Placebo
Comments The mean change from baseline in PedMIDAS score over time for the three groups was assessed using a linear regression model for each of the three pairwise comparisons (Amitriptyline relative to placebo, Topiramate relative to placebo, and Amitriptyline relative to Topiramate), adjusted for the baseline PedMIDAS score. The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1331
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -4.84
Confidence Interval (2-Sided) 95%
-11.16 to 1.49
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Topiramate, Amitriptyline
Comments The mean change from baseline in PedMIDAS score over time for the three groups was assessed using a linear regression model for each of the three pairwise comparisons (Amitriptyline relative to placebo, Topiramate relative to placebo, and Amitriptyline relative to Topiramate), adjusted for the baseline PedMIDAS score. The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1011
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.49
Confidence Interval (2-Sided) 95%
-0.88 to 9.87
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Number of Headache Days
Hide Description

This outcomes measure examines whether the rate of absolute number of headache days, per 28 day period, differs between treatment groups over time. This was assessed longitudinally based on the actual number of headache days from the 28 days prior to randomization to the last 28 days of this 24 week trial. The change in absolute headache days was compared between:

  1. Amitriptyline vs. placebo
  2. Topiramate vs. placebo
  3. Amitriptyline vs. Topiramate
Time Frame 4 week baseline period and last 4 weeks of the 24-week trial
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who had observed end-point data: 101 in the topiramate group, 59 in the placebo group, and104 in the amitriptyline group.
Arm/Group Title Topiramate Placebo Amitriptyline
Hide Arm/Group Description:
Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms).
Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Overall Number of Participants Analyzed 101 59 104
Mean (Standard Deviation)
Unit of Measure: days
-6.7  (4.99) -5.9  (6.96) -6.7  (6.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Amitriptyline
Comments Another major secondary objective was to determine if the change in absolute headache days from baseline to week 24 differed between treatment groups. This objective was assessed using linear regression models, with three pairwise comparisons between treatment groups (Amitriptyline vs. Placebo, Topiramate vs. Placebo, and Amitriptyline vs. Topiramate). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3553
Comments Each comparison was tested using a Bonferroni corrected significance level of 0.017 (0.05/3).
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.72
Confidence Interval (2-Sided) 98.3%
-2.59 to 1.15
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Topiramate, Placebo
Comments Another major secondary objective was to determine if the change in absolute headache days from baseline to week 24 differed between treatment groups. This objective was assessed using linear regression models, with three pairwise comparisons between treatment groups (Amitriptyline vs. Placebo, Topiramate vs. Placebo, and Amitriptyline vs. Topiramate). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4143
Comments Each comparison was tested using a Bonferroni corrected significance level of 0.017 (0.05/3).
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.64
Confidence Interval (2-Sided) 98.3%
-2.52 to 1.24
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Topiramate, Amitriptyline
Comments Another major secondary objective was to determine if the change in absolute headache days from baseline to week 24 differed between treatment groups. This objective was assessed using linear regression models, with three pairwise comparisons between treatment groups (Amitriptyline vs. Placebo, Topiramate vs. Placebo, and Amitriptyline vs. Topiramate). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9038
Comments Each comparison was tested using a Bonferroni corrected significance level of 0.017 (0.05/3).
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.08
Confidence Interval (2-Sided) 98.3%
-1.68 to 1.52
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Tolerability, as Indicated by the Number (Percentage) of Participants That Completed the 24-week Treatment Phase
Hide Description To assess tolerability, the percentage of subjects who complete the entire 24-week treatment period will be estimated in each of the three groups.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Tolerability was assessed for all participants included in the primary analysis. Of those randomized, 33 were not included in the primary analysis due to early trial closure.
Arm/Group Title Topiramate Placebo Amitriptyline
Hide Arm/Group Description:
Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms).
Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Overall Number of Participants Analyzed 130 66 132
Measure Type: Count of Participants
Unit of Measure: Participants
102
  78.5%
59
  89.4%
106
  80.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Amitriptyline
Comments Tolerability was assessed by calculating the percent of subjects who completed the entire 24 week treatment period and the corresponding 95% confidence intervals for each treatment group. Concerns regarding tolerability would be raised if the upper bound of a confidence interval was less than 65% or if the percent of subjects who completed the entire 24 week treatment period in either of the active treatment groups was significantly less than the placebo group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1557
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.07
Confidence Interval (2-Sided) 95%
0.85 to 5.05
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Topiramate, Placebo
Comments Tolerability was assessed by calculating the percent of subjects who completed the entire 24 week treatment period and the corresponding 95% confidence intervals for each treatment group. Concerns regarding tolerability would be raised if the upper bound of a confidence interval was less than 65% or if the percent of subjects who completed the entire 24 week treatment period in either of the active treatment groups was significantly less than the placebo group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0754
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.31
Confidence Interval (2-Sided) 95%
0.95 to 5.62
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Topiramate, Amitriptyline
Comments Tolerability was assessed by calculating the percent of subjects who completed the entire 24 week treatment period and the corresponding 95% confidence intervals for each treatment group. Concerns regarding tolerability would be raised if the upper bound of a confidence interval was less than 65% or if the percent of subjects who completed the entire 24 week treatment period in either of the active treatment groups was significantly less than the placebo group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7611
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.49 to 1.62
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Occurrence of Treatment Emergent Serious Adverse Events
Hide Description To determine if amitriptyline or topiramate differ from placebo on the occurrence of treatment emergent serious adverse events.
Time Frame 24 weeks of the trial
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Topiramate Placebo Amitriptyline
Hide Arm/Group Description:
Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms).
Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Overall Number of Participants Analyzed 145 72 144
Measure Type: Number
Unit of Measure: serious adverse events
4 2 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Amitriptyline
Comments The occurrence of treatment-related SAE’s was assessed in two ways: 1) percentage of subjects who experience any treatment-related SAE in each of the three groups was compared using Fishers exact test; 2) rates of treatment-emergent SAS’s across the three groups were compared using a Poisson regression model. However, due to the small number of SAEs that were deemed treatment-emergent (4 in AMI, 1 in TPM, 0 in PBO), the parameter estimates did not converge for the Poisson regression model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3038
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Topiramate, Placebo
Comments The occurrence of treatment-related SAE’s was assessed in two ways: 1) percentage of subjects who experience any treatment-related SAE in each of the three groups was compared using Fishers exact test; 2) rates of treatment-emergent SAS’s across the three groups were compared using a Poisson regression model. However, due to the small number of SAEs that were deemed treatment-emergent (4 in AMI, 1 in TPM, 0 in PBO), the parameter estimates did not converge for the Poisson regression model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Topiramate, Amitriptyline
Comments The occurrence of treatment-related SAE’s was assessed in two ways: 1) percentage of subjects who experience any treatment-related SAE in each of the three groups was compared using Fishers exact test; 2) rates of treatment-emergent SAS’s across the three groups were compared using a Poisson regression model. However, due to the small number of SAEs that were deemed treatment-emergent (4 in AMI, 1 in TPM, 0 in PBO), the parameter estimates did not converge for the Poisson regression model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2139
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame Adverse events were collected after the ingestion of at least one dose of study drug through study completion, an average of 24 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Topiramate Placebo Amitriptyline
Hide Arm/Group Description Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved. Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms). Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
All-Cause Mortality
Topiramate Placebo Amitriptyline
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Topiramate Placebo Amitriptyline
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/145 (2.76%)      2/72 (2.78%)      6/144 (4.17%)    
Gastrointestinal disorders       
Intussusception  1  1/145 (0.69%)  1 0/72 (0.00%)  0 0/144 (0.00%)  0
Immune system disorders       
Anaphylactic reaction  1  0/145 (0.00%)  0 0/72 (0.00%)  0 1/144 (0.69%)  1
Infections and infestations       
Appendicitis  1  0/145 (0.00%)  0 1/72 (1.39%)  1 0/144 (0.00%)  0
Pharyngitis streptococcal  1  0/145 (0.00%)  0 1/72 (1.39%)  1 0/144 (0.00%)  0
Injury, poisoning and procedural complications       
Contusion  1  1/145 (0.69%)  1 0/72 (0.00%)  0 0/144 (0.00%)  0
Traumatic Liver Injury  1  1/145 (0.69%)  1 0/72 (0.00%)  0 0/144 (0.00%)  0
Nervous system disorders       
Syncope  1  0/145 (0.00%)  0 0/72 (0.00%)  0 1/144 (0.69%)  1
Psychiatric disorders       
Suicide attempt  1  1/145 (0.69%)  1 0/72 (0.00%)  0 0/144 (0.00%)  0
Mood altered  1  0/145 (0.00%)  0 0/72 (0.00%)  0 3/144 (2.08%)  3
Respiratory, thoracic and mediastinal disorders       
Bronchospasm  1  0/145 (0.00%)  0 0/72 (0.00%)  0 1/144 (0.69%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Topiramate Placebo Amitriptyline
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   111/145 (76.55%)      51/72 (70.83%)      106/144 (73.61%)    
Gastrointestinal disorders       
Dry Mouth  1  26/145 (17.93%)  30 9/72 (12.50%)  9 36/144 (25.00%)  45
General disorders       
Fatigue  1  36/145 (24.83%)  40 10/72 (13.89%)  12 43/144 (29.86%)  48
Infections and infestations       
Streptococcal Pharyngitis  1  1/145 (0.69%)  1 3/72 (4.17%)  3 7/144 (4.86%)  7
Upper Respiratory Tract Infection  1  18/145 (12.41%)  19 10/72 (13.89%)  10 14/144 (9.72%)  16
Investigations       
Decreased Weight  1  11/145 (7.59%)  11 0/72 (0.00%)  0 0/144 (0.00%)  0
Nervous system disorders       
Asphasia  1  23/145 (15.86%)  25 7/72 (9.72%)  9 13/144 (9.03%)  16
Cognitive Disorder  1  23/145 (15.86%)  25 8/72 (11.11%)  8 14/144 (9.72%)  18
Dizziness  1  9/145 (6.21%)  9 1/72 (1.39%)  2 3/144 (2.08%)  3
Memory Impairment  1  24/145 (16.55%)  29 7/72 (9.72%)  8 11/144 (7.64%)  11
Paresthesia  1  45/145 (31.03%)  67 6/72 (8.33%)  6 10/144 (6.94%)  10
Psychiatric disorders       
Mood Altered  1  14/145 (9.66%)  16 4/72 (5.56%)  4 8/144 (5.56%)  8
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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
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Name/Title: Scott Powers, PhD
Organization: Cincinnati Children's Hospital Medical Center
Phone: 513-636-8106
EMail: scott.powers@cchmc.org
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01581281     History of Changes
Other Study ID Numbers: CIN-001
1U01NS076788-01 ( U.S. NIH Grant/Contract )
First Submitted: December 16, 2011
First Posted: April 20, 2012
Results First Submitted: November 16, 2016
Results First Posted: August 10, 2017
Last Update Posted: August 10, 2017