NINDS CRC Chronic Migraine Treatment Trial

Study Overview
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Brief Summary
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The purpose of this study is to compare the reduction in the number of severe headache days at six months in people with chronic migraine treated with topiramate and propranolol versus those treated with topiramate and a placebo.

Detailed Description
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Chronic migraine affects about 2 percent of all adults. Currently there are no effective preventative treatments to deal with this disabling condition. Three randomized, placebo-controlled trials found that topiramate was an effective, safe and generally well-tolerated drug for treating chronic migraine. As a result of these trials, topiramate is becoming the standard treatment among headache specialists. Experts agree that treatment with combinations of preventive agents is required in the majority of individuals with chronic migraine for maximal headache relief. No randomized trials have assessed the value of frequently used combinations of preventive agents for chronic migraine. The goal of this trial is to determine if adding a second drug to topiramate treatment will further reduce the headache burden for people with this condition. In the study, 250 participants with chronic migraine will be randomized to two groups - treatment with topiramate and propranolol or topiramate and placebo. Participants will be followed for six months.

Official Title
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NINDS Clinical Research Collaboration Chronic Migraine Treatment Trial

Conditions
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Chronic Migraine

Intervention / Treatment
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* Drug: propranolol LA
* Drug: topiramate
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of chronic migraine for at least 6 months Age ≥ 18 years and age of migraine onset 60 or younger EKG performed in the last 12 months Exclusion Criteria: Prior neuro-imaging suggesting secondary structural causes of headache Beck Depression Inventory FastScreen score of 13 or greater or other severe psychiatric disorder Contraindication to or prior intolerance of topiramate or propranolol (no history of sinus bradycardia, heart block, heart failure, diabetes prone to hypoglycemia, asthma, kidney stones) History of kidney failure or nephrolithiasis A female who is currently pregnant or lactating or planning to become pregnant in the next year, or is of child-bearing potential and not practicing an acceptable form of birth control Currently requires butalbital or opioid drugs for acute headache treatment 10 or more days a month Failure of prior trials with at least 50 mg of topiramate combined with at least 80 mg of propranolol Use of other migraine preventive drugs (Medications graded as groups 1, 2, 3, and 4 in the AAN Evidence-based Guideline: valproate, divalproex sodium, gabapentin, amitriptyline, nortriptyline, protriptyline, beta-blocker, calcium channel blocker, cyproheptadine; and tizanidine) within the last two months or has received botulinum toxin injection in the past 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Participants will receive propranolol and topiramate. | Drug: propranolol LA<br>* Propranolol LA up to 240 mg/day<br>* Other names: Inderal LA;Drug: topiramate<br>* Topiramate is an effective, safe and generally well-tolerated drug used for treating chronic migraine. It is becoming the standard treatment among headache specialists.<br>|
| Placebo Comparator: 2<br>Participants will receive a placebo and topiramate. | Drug: topiramate<br>* Topiramate is an effective, safe and generally well-tolerated drug used for treating chronic migraine. It is becoming the standard treatment among headache specialists.<br>Drug: placebo<br>* an inactive substance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Number of Moderate to Severe Headache Days Within a 28 Day Average Period in Six Months Compared to Baseline | (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). | Baseline (pre-randomization), months 5 and 6 post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing at Least a 30% Reduction in 28-day Moderate to Severe Headache Days |  | 6 months post randomization | 
| Number of Subjects Experiencing at Least a 50% Reduction in 28-day Moderate to Severe Headache Days |  | 6 months | 
| Change From Baseline in Beck's Depression Inventory FastScreen Score at 6 Months | 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). | Baseline and 6 months | 
| Change From Baseline in Migraine Disability Assessment (MIDAS) Score at 6 Months | 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). | Baseline and 6 months | 
| Change From Baseline in Migraine Specific Quality of Life (MSQ)-Role Restrictive Score at 6 Months | 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. | baseline and 6 months post randomization | 
| Change From Baseline in Migraine-Specific Quality of Life (MSQ)-Role Preventive at 6 Months | 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. | Baseline and 6 months | 
| Change From Baseline in Migraine-Specific Quality of Life (MSQ) - Emotional Function at 6 Months | 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. | Baseline and 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic migraine, migraine prevention, chronic headache