Metformin for the Prevention of Episodic Migraine (MPEM) (MPEM)

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

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

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Metformin; Drug: Matching Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age 18-65 years
2. a diagnosis of migraine with or without aura for >1 year according to the International Classification of Headache Disorders-IIIb

Exclusion Criteria:

1. a diagnosis of diabetes mellitus or polycystic ovarian syndrome
2. overuse of acute migraine treatments
3. failure to respond to 3 or more classes of preventive drug treatments
4. change in dose of migraine-preventive medication within 2 months of beginning the baseline diary phase
5. significant somatic or psychiatric disease
6. known alcohol or other substance abuse
7. pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin first, then matching placebo; 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; Metformin 500mg twice daily; Drug: Matching Placebo; Matching Placebo twice daily; Other Names: Placebo
Experimental: Matching placebo first, then Metformin; 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; Metformin 500mg twice daily; Drug: Matching Placebo; Matching Placebo twice daily; Other Names: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Amaal J Starling, MD, Mayo Clinic

Publications and helpful links

General Publications

• Price TJ, Dussor G. AMPK: An emerging target for modification of injury-induced pain plasticity. Neurosci Lett. 2013 Dec 17;557 Pt A(0 0):9-18. doi: 10.1016/j.neulet.2013.06.060. Epub 2013 Jul 3.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: October 28, 2015
• First Submitted That Met QC Criteria: October 29, 2015
• First Posted (Estimate): October 30, 2015

Study Record Updates

• Last Update Posted (Actual): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 15, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 15-000422

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No