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NCT Number: NCT06808230

Cocoa Extract for Migraine Trial

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

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location status: Recruiting

Location contact

Pamela M Rist, ScD

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

Cocoa extract

Dietary Supplement

Cocoa extract manufactured as 250 mg capsules

Cocoa extract placebo

Dietary Supplement

Cocoa extract placebo

Primary outcomes

  1. Recruitment

    Time frame: 15 months

    We will be able to recruit and randomize 114 eligible individuals

  2. Retention

    Time frame: From run-in to end of treatment at 12 weeks

    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

  3. Adherence

    Time frame: 12 week intervention period

    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)

Secondary outcomes

  1. Migraine days

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

    Number of migraine attacks as recorded in migraine diaries

  2. Responder rate

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

    Proportion of individuals who experience a ≥50% reduction in migraine days

  3. Migraine severity

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

    Four-point scale with categories of "absent, mild, moderate, or severe".

  4. Adverse events

    Time frame: 12 week intervention period

    Potential side effects and adverse events

  5. Reports of worsening of migraine symptoms

    Time frame: 12 week intervention period

    Worsening of photophobia, phonophobia, or osmophobia, and worsening of aura symptoms in the past week compared to the week prior

  6. Allodynia Symptom Checklist

    Time frame: Baseline and end of the 12 week intervention period

    Survey assessing how often individuals with migraine experience allodynia

  7. Headache Related Disability (HIT-6)

    Time frame: Baseline and end of the 12 week intervention period

    Evaluates the impact headaches have on a patient's life and

  8. PROMIS-29

    Time frame: Baseline and end of the 12 week intervention period

    Measures of patient-reported health status for physical, mental, and social well-being

  9. Urine levels of gamma-valerolactone metabolites (gVLM)

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

    Biomarker of dietary flavanol intake

Study contacts

Contact information is provided by the study sponsor or research team.

Pamela M Rist, ScD

CONTACT

[email protected]

877-517-2555

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • National Center for Complementary and Integrative Health (NCCIH)

Registry information

Official study title

Cocoa Flavanols for Migraine: A Pilot Study

Acronym: CORAL

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Feb 5, 2025
Registry last updated
Jun 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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