Cocoa Extract for Migraine Trial

NCT06808230 | Recruiting DMC

• 2 other identifiers: 2024P003655U01AT012611
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to assess the feasibility of recruitment and adherence to a high-dose cocoa extract supplement in individuals diagnosed with episodic migraine. The main questions it aims to answer are:

• Will we be able to enroll 114 participants during the recruitment period?
• Will participants take study pills daily during the pill-taking period? Researchers will compare two doses of cocoa extract to placebo to determine the acceptability of higher doses of cocoa extract supplementation in this patient population. Participants will be asked to:
• Provide two urine samples
• Complete daily questionnaires
• Take four study pills a day for 12 weeks

Conditions

Migraine

Keywords

migraine; cocoa extract; cocoa flavanol

Outcome Measures

Primary Outcomes (3)

• Recruitment

  We will be able to recruit and randomize 114 eligible individuals

  15 months

• Retention

  Retention will be quantified by the proportion of subjects who record their migraines for at least 22 out of 28 days during run-in and the last four weeks of the intervention and complete all questionnaires at baseline and follow-up

  From run-in to end of treatment at 12 weeks

• Adherence

  Adherence will be calculated as the proportion of participants who miss no more than 12 days of study pills (i.e. participants will consume study pills on 85% of the intervention days)

  12 week intervention period

Secondary Outcomes (9)

• Migraine days

  Four week run-in period and final four weeks of the 12 week intervention period

• Responder rate

  Four week run-in period and final four weeks of the 12 week intervention period

• Migraine severity

  Four week run-in period and final four weeks of the 12 week intervention period

• Adverse events

  12 week intervention period

• Reports of worsening of migraine symptoms

  12 week intervention period

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants assigned to this arm will take four placebo pills per day.

Dietary Supplement: Cocoa extract placebo

500 mg cocoa extract

EXPERIMENTAL

Participants assigned to this arm will take two 250 mg cocoa extract pills per day and two placebo pills per day

Dietary Supplement: Cocoa extract

1000 mg cocoa extract

EXPERIMENTAL

Participants assigned to this arm will take four 250 mg cocoa extract pills per day

Dietary Supplement: Cocoa extract

Interventions

Cocoa extract DIETARY_SUPPLEMENT

Cocoa extract manufactured as 250 mg capsules

1000 mg cocoa extract; 500 mg cocoa extract

Cocoa extract placebo DIETARY_SUPPLEMENT

Cocoa extract placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and men aged ≥18 years
• Self-reported clinician diagnosis of migraine with or without aura which does not meet criteria for chronic migraine (according to the International Classification of Headache Disorders 3rd edition)
• Individuals with self-reported migraine will need to report a clinician diagnosis of migraine and be classified as having migraine or probable migraine by the American Migraine Study (AMS) migraine screener. The AMS migraine screener, which has a sensitivity of 100% and a specificity of 82% for the diagnosis of migraine will be used to confirm self-reported migraine status.
• History of migraine dating for at least one year
• Self-report of 4 to 14 migraine attacks during the 30 days prior to enrollment in the study
• Completion of at least 22 headache diary days during the 28 day run-in period
• o Report migraine frequency between 4 to 14 days during the 28 day run-in period
• If currently using medications to prevent or treat migraine, no new medication use within the past 3 months
• No new use of behavioral interventions within the past 3 months and/or agree to not begin new behavioral interventions during this trial
• Be willing to complete all study procedures and be randomized to all interventional groups
• Be fluent in English
• Own an iPhone or Android device and be willing to download MyCap to the device

You may not qualify if:

• Self-reported history of stroke or transient ischemic attack; history of brain surgery or spine surgery; currently receiving treatment for a concussion; and self-reported diagnosis of cluster headache, brain tumor, brain aneurysm, traumatic brain injury, multiple sclerosis, epilepsy, schizophrenia, or bipolar disorder
• Kidney failure or current dialysis treatment or any medical condition which the participant believes could lead to difficulty complying with the protocol
• Current alcohol or substance abuse (self-reported)
• Self-reported clinician diagnosis of medication overuse headache
• Currently or recently (past 6 months) received Botox treatment for migraine
• Failure to return the baseline urine sample
• Currently pregnant, nursing, or intending to become pregnant during the study period.
• Unwilling to forgo use of out-of-study supplements of cocoa extract during the trial
• Extreme sensitivity to caffeine

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Migraine Disorders

Interventions

Chocolate

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Pamela M Rist, ScD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pamela M Rist, ScD

CONTACT

877-517-2555; bwhcoral@mgb.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Epidemiologist

Study Record Dates

• First Submitted: January 29, 2025
• First Posted: February 5, 2025
• Study Start: June 23, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Data will be shared no later than time of the final publication of study results or the end of the performance period, whichever comes first. The duration of preservation and sharing of the data will be a minimum of 10 years after the end of the funding period.
• Access Criteria: Data and supporting materials will be shared on the Harvard Dataverse. The data that is shared will be shared by unrestricted download.

Locations

US (1)