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NINDS CRC Chronic Migraine Treatment Trial (CMTT)

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ClinicalTrials.gov Identifier: NCT00772031
Recruitment Status : Completed
First Posted : October 15, 2008
Results First Posted : January 19, 2012
Last Update Posted : January 24, 2012
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Ortho-McNeil Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Anne Lindblad, The EMMES Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Chronic Migraine
Interventions Drug: propranolol LA
Drug: topiramate
Drug: placebo
Enrollment 191

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo
Hide Arm/Group Description Participants will receive propranolol and topiramate. Participants will receive a placebo and topiramate.
Period Title: Overall Study
Started 96 95
Completed 64 52
Not Completed 32 43
Reason Not Completed
Early termination of trial             12             10
Lost to Follow-up             20             33
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo Total
Hide Arm/Group Description Participants will receive propranolol and topiramate. Participants will receive a placebo and topiramate. Total of all reporting groups
Overall Number of Baseline Participants 96 95 191
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants 95 participants 191 participants
<=18 years
2
   2.1%
1
   1.1%
3
   1.6%
Between 18 and 65 years
94
  97.9%
92
  96.8%
186
  97.4%
>=65 years
0
   0.0%
2
   2.1%
2
   1.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 96 participants 95 participants 191 participants
39.8  (1.09) 41.2  (1.15) 40.5  (0.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants 95 participants 191 participants
Female
84
  87.5%
88
  92.6%
172
  90.1%
Male
12
  12.5%
7
   7.4%
19
   9.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 96 participants 95 participants 191 participants
96 95 191
1.Primary Outcome
Title Change in the Number of Moderate to Severe Headache Days Within a 28 Day Average Period in Six Months Compared to Baseline
Hide Description (Number of moderate to severe headache days (as defined by the International Headache Society Guidelines (2006)) counted over a 28 day diary period at baseline (before treatment with propranolol or placebo)) minus (the number of moderate to severe headache days counted over a 56 day diary period (weeks 16-24 post treatment) divided by 2).
Time Frame Baseline (pre-randomization), months 5 and 6 post randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT to the extent diary information was available. Available defined as all subjects with 12 or more diary entries between 16 and 24 weeks. Multiple imputation used on all randomized subjects as a sensitivity analysis on the primary outcome.
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo
Hide Arm/Group Description:
Participants will receive propranolol and topiramate.
Participants will receive placebo and topiramate.
Overall Number of Participants Analyzed 63 48
Mean (Standard Deviation)
Unit of Measure: Moderate to severe headache days
4.4  (5.98) 4.7  (5.66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Topiramate Plus Propranolol, Topiramate Plus Placebo
Comments The study was designed to enroll 250 subjects to provide at least 90% power to detect a 3-day difference and 87% power to detect a 2.5-day difference in 28-day moderate-to-severe headache rate reductions at six months, assuming a type I error rate of 0.05, a two-sided test, a 10% loss to follow-up and a standard deviation of within-person change in days with headache of six.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.77
Comments [Not Specified]
Method ANCOVA
Comments covariate adjustments: study site, baseline mod-to-sev 28-day headache-rate, topiramate use, medication overuse, and anti-depressive medications use.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.8 to 2.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.97
Estimation Comments Topiramate plus placebo mean reduction minus topiramate plus propranolol reduction
2.Secondary Outcome
Title Number of Subjects Experiencing at Least a 30% Reduction in 28-day Moderate to Severe Headache Days
Hide Description [Not Specified]
Time Frame 6 months post randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects randomized with opportunity for 6 month followup. Due to early study termination those who did not have opportunity for 6 month followup at time of study closure were excluded. All lost to followups were counted as failure
Arm/Group Title Topiramate Plus Proporanolol Topiramate Plus Placebo
Hide Arm/Group Description:
Participants will receive propranolol and topiramate.
Participants will receive placebo and topiramate.
Overall Number of Participants Analyzed 84 82
Measure Type: Number
Unit of Measure: participants
37 28
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Topiramate Plus Proporanolol, Topiramate Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
0.75 to 2.78
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Subjects Experiencing at Least a 50% Reduction in 28-day Moderate to Severe Headache Days
Hide Description [Not Specified]
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants with the opportunity for 6-month follow-up. Due to early study termination some participants were randomized and did not have the opportunity to be followed for six months
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo
Hide Arm/Group Description:
Participants will receive propranolol and topiramate.
Participants will receive placebo and topiramate.
Overall Number of Participants Analyzed 84 82
Measure Type: Number
Unit of Measure: participants
26 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Topiramate Plus Propranolol, Topiramate Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.00
Confidence Interval 95%
0.50 to 2.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Beck's Depression Inventory FastScreen Score at 6 Months
Hide Description Total score from Beck's Depression Inventory FastScreen at 6 months minus total score from Beck's Depression Inventory FastScreen at baseline. Scale scores range from 0 to 21 with higher values indicating worsening depression. the following categories separate participants into groups of depression levels: Minimal (Score 0-3), Mild (Score 4-8),Moderate (Score 9-12),Severe (Score 13-21).
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number who completed the Beck's Depression Inventory at baseline and three months
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo
Hide Arm/Group Description:
Participants will receive propranolol and topiramate.
Participants will receive a placebo and topiramate.
Overall Number of Participants Analyzed 53 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.3  (0.25) 0.6  (0.30)
5.Secondary Outcome
Title Change From Baseline in Migraine Disability Assessment (MIDAS) Score at 6 Months
Hide Description MIDAS scoring ranges from 0 to 270. The scores are divided into ranges of disability with higher scores indicating increased disability as follows: 0-5 (Grade I - Minimal or infrequent disability); 6-10 (Grade II - Mild or infrequent disability); 11-20 (Grade III - Moderate disability); and 21+ (Grade IV - Severe disability).
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
per protocol
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo
Hide Arm/Group Description:
Participants will receive propranolol and topiramate.
Participants will receive a placebo and topiramate.
Overall Number of Participants Analyzed 53 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
-3.18  (3.70) -3.46  (3.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Topiramate Plus Propranolol, Topiramate Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.91
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.28
Parameter Dispersion
Type: Standard Deviation
Value: 3.75
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Migraine Specific Quality of Life (MSQ)-Role Restrictive Score at 6 Months
Hide Description The MSQ (version 2.1 copyrighted 1992, 1996, 1998 by Glaxo Wellcome Inc., Research Triangle Park, North Carolina) is a 14 item questionnaire. Item responses are summed and scored as a total score and three domains: Role Preventive, Role Restrictive, Emotional Function. Scores within each domain are rescaled to range from 0 to 100. A lower score indicates a poorer quality of life associated with that domain or in total. Because of the observed interaction within a domain, only domain scores were used as outcome measures for this study.
Time Frame baseline and 6 months post randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
per protocol
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo
Hide Arm/Group Description:
Participants will receive propranolol and topiramate.
Participants will receive a placebo and topiramate.
Overall Number of Participants Analyzed 53 62
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.7  (5.5) -2.2  (5.71)
7.Secondary Outcome
Title Change From Baseline in Migraine-Specific Quality of Life (MSQ)-Role Preventive at 6 Months
Hide Description The MSQ (version 2.1 copyrighted 1992, 1996, 1998 by Glaxo Wellcome Inc., Research Triangle Park, North Carolina) is a 14 item questionnaire. Item responses are summed and scored as a total score and three domains: Role Preventive, Role Restrictive, Emotional Function. Scores within each domain are rescaled to range from 0 to 100. A lower score indicates a poorer quality of life associated with that domain or in total. Because of the observed interaction within a domain, only domain scores were used as outcome measures for this study.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Topiramate Plus Propranolol, no Prior, Stable Topiramate Topiramate Plus Placebo, no Prior, Stable Topiramate Topiramate Plus Propranolol, Prior, Stable Topiramate Topiramate Plus Placebo, Prior, Stable Topiramate
Hide Arm/Group Description:
Participants without prior stable topiramate use received propranolol and topiramate.
Participants without prior stable topiramate use received a placebo and topiramate.
Participants with prior stable topiramate use received propranolol and topiramate.
Participants with prior stable topiramate use received a placebo and topiramate.
Overall Number of Participants Analyzed 40 31 13 13
Mean (Standard Deviation)
Unit of Measure: units on a scale
12.9  (2.88) 5.9  (3.10) -11.5  (5.00) 11.0  (5.06)
8.Secondary Outcome
Title Change From Baseline in Migraine-Specific Quality of Life (MSQ) - Emotional Function at 6 Months
Hide Description The MSQ (version 2.1 copyrighted 1992, 1996, 1998 by Glaxo Wellcome Inc., Research Triangle Park, North Carolina) is a 14 item questionnaire. Item responses are summed and scored as a total score and three domains: Role Preventive, Role Restrictive, Emotional Function. Scores within each domain are rescaled to range from 0 to 100. A lower score indicates a poorer quality of life associated with that domain or in total. Because of the observed interaction within a domain, only domain scores were used as outcome measures for this study.
Time Frame Baseline and 6 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo
Hide Arm/Group Description:
Participants will receive propranolol and topiramate.
Participants will receive a placebo and topiramate.
Overall Number of Participants Analyzed 53 62
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.9  (3.43) 9.8  (3.80)
Time Frame 6 months
Adverse Event Reporting Description Self report and systematic questions at scheduled visits(Tingling or prickling;Nausea/Vomiting;Weight loss;Weight gain;More than usual fatigue;Depression;Trouble thinking;New or unusual problems with memory;Racing, pounding or skipping of heart(more than 1 time);Dizziness(more than 1 time);Impotence).
 
Arm/Group Title Topiramate Plus Propranolol Topiramate Plus Placebo
Hide Arm/Group Description Participants will receive propranolol and topiramate. Participants will receive a placebo and topiramate.
All-Cause Mortality
Topiramate Plus Propranolol Topiramate Plus Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Topiramate Plus Propranolol Topiramate Plus Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/96 (7.29%)      5/95 (5.26%)    
Gastrointestinal disorders     
Upper Abdominal Pain * 1  1/96 (1.04%)  1 0/95 (0.00%)  0
Vomiting  2  0/96 (0.00%)  0 1/95 (1.05%)  1
Injury, poisoning and procedural complications     
Overdose  1  1/96 (1.04%)  1 0/95 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration * 1  1/96 (1.04%)  1 0/95 (0.00%)  0
Nervous system disorders     
Paraesthesia  1  1/96 (1.04%)  1 0/95 (0.00%)  0
Headache  2  1/96 (1.04%)  1 0/95 (0.00%)  0
Syncope  2  1/96 (1.04%)  1 0/95 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Pregnancy * 2  0/96 (0.00%)  0 2/95 (2.11%)  2
Psychiatric disorders     
Insomnia * 1  1/96 (1.04%)  1 0/95 (0.00%)  0
Depression  2  1/96 (1.04%)  2 0/95 (0.00%)  0
Reproductive system and breast disorders     
Breast Pain * 1  0/96 (0.00%)  0 1/95 (1.05%)  1
Breast Mass * 2  0/96 (0.00%)  0 1/95 (1.05%)  1
Pelvic Pain * 2  0/96 (0.00%)  0 1/95 (1.05%)  1
Respiratory, thoracic and mediastinal disorders     
Respiratory Tract Congestion * 2  1/96 (1.04%)  1 0/95 (0.00%)  0
Surgical and medical procedures     
Colporrhaphy * 2  0/96 (0.00%)  0 1/95 (1.05%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA(13.0)
2
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Topiramate Plus Propranolol Topiramate Plus Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   59/96 (61.46%)      50/95 (52.63%)    
General disorders     
Fatigue  1  22/96 (22.92%)  11/95 (11.58%) 
Nervous system disorders     
Dizziness  1  13/96 (13.54%)  3/95 (3.16%) 
Memory Impairment  1  6/96 (6.25%)  8/95 (8.42%) 
Mental Impairment  1  12/96 (12.50%)  7/95 (7.37%) 
Paraesthesia  1  12/96 (12.50%)  10/95 (10.53%) 
Psychiatric disorders     
Depression  1  8/96 (8.33%)  3/95 (3.16%) 
Insomnia * 1  2/96 (2.08%)  7/95 (7.37%) 
Vascular disorders     
Any Vascular Disorder * 1  5/96 (5.21%)  3/95 (3.16%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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
Name/Title: Anne S Lindblad, PhD
Organization: The EMMES Corporation
Phone: 301 251 1161 ext 105
Responsible Party: Anne Lindblad, The EMMES Corporation
ClinicalTrials.gov Identifier: NCT00772031     History of Changes
Other Study ID Numbers: 08-CRC-01
HHSN265200523641C ( Other Identifier: NINDS Contract )
First Submitted: October 14, 2008
First Posted: October 15, 2008
Results First Submitted: October 18, 2011
Results First Posted: January 19, 2012
Last Update Posted: January 24, 2012