Metformin for the Prevention of Episodic Migraine (MPEM)

Study Overview
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Brief Summary
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The investigators will evaluate the safety and efficacy of metformin for preventive treatment of migraine in a randomized, double-blind, placebo-controlled, crossover trial.

Detailed Description
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This will be a single-center, double-blind, randomized, placebo-controlled, crossover study. The investigators will enroll 40 subjects. Subjects will be recruited from the outpatient Mayo Headache Clinic, Mayo Women's Health Clinic, Mayo Community Internal Medicine, and the Mayo Clinic- Arizona State University Neurology Clinic. The Headache Clinic employs 6 headache specialists and 1 fellow which is sufficient staffing to support this study and recruitment of patients with migraine. Before study enrollment, patients will undergo a 2-hour oral glucose tolerance test to confirm the absence of diabetes mellitus. Subjects will then keep a headache diary for 4 weeks to establish baseline characteristics, including number of migraine days per month, number of moderate to severe headache days per month, and number of days per month of acute medication use. The 4-week baseline period will be followed by 2 treatment periods of 12 weeks each, separated by a washout period of 4 weeks (total study duration, 32 weeks). For the 12-week treatment periods, subjects will receive either metformin 500mg twice daily or matching placebo twice daily. Subjects will have 7 study visits. Routine laboratory studies and a pregnancy test will be performed at enrollment and week 20. Abnormal kidney or liver function will exclude subjects. Pregnancy will exclude subjects. General and neurologic examinations will be performed during 3 of the 7 visits. At each visit, subjects will receive medication for the period until the next visit. A headache diary will be used for the trial. For every day that the subject has a headache of any type, she or he will record headache characteristics, associated features, and medications used.

Official Title
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Metformin for the Prevention of Episodic Migraine: a Randomized, Double-blind, Placebo-controlled, Crossover Study

Conditions
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Migraine

Intervention / Treatment
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* Drug: Metformin
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-65 years a diagnosis of migraine with or without aura for >1 year according to the International Classification of Headache Disorders-IIIb Exclusion Criteria: a diagnosis of diabetes mellitus or polycystic ovarian syndrome overuse of acute migraine treatments failure to respond to 3 or more classes of preventive drug treatments change in dose of migraine-preventive medication within 2 months of beginning the baseline diary phase significant somatic or psychiatric disease known alcohol or other substance abuse pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin first, then matching placebo<br>Subjects will be randomized into the Metformin group, treated for 12 weeks with a 4 week washout period in between treatments, then treated with matching placebo for 12 weeks. | Drug: Metformin<br>* Metformin 500mg twice daily<br>Drug: Matching Placebo<br>* Matching Placebo twice daily<br>* Other names: Placebo;|
| Experimental: Matching placebo first, then Metformin<br>Subjects will be randomized into the matching placebo group, treated for 12 weeks with a 4 week washout period in between treatments, then treated with Metformin for 12 weeks. | Drug: Metformin<br>* Metformin 500mg twice daily<br>Drug: Matching Placebo<br>* Matching Placebo twice daily<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache Days | Total number of moderate and severe headache days | Baseline through end of study for a total of approximately 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Greater Than >50% Reduction in Migraine Days on Metformin | Percentage of patients whose migraines reduced by at least 50% on Metformin. | 12 weeks | 
| Adverse Events | Total number of subjects with treatment-related adverse events | Baseline through end of study for a total of approximately 32 weeks |