The COCOA-PAD II Trial

Last updated: May 12, 2025
Sponsor: Northwestern University
Overall Status: Active - Recruiting

Phase

3

Condition

Claudication

Peripheral Arterial Occlusive Disease

Thrombosis

Treatment

cocoa flavanols

placebo

Clinical Study ID

NCT04794530
STU00213897
R01AG068458-01A1
  • Ages > 55
  • All Genders

Study Summary

Among people with peripheral artery disease (PAD) age 55 and older, the investigators will test the hypothesis that PAD participants randomized to cocoa flavanols will have greater improvement or less decline in six-minute walk distance at six-month follow-up, compared to those randomized to placebo. The study will randomize 190 participants with PAD age 55 and older to one of two groups for six months: cocoa flavanols vs placebo. Our primary outcome is change in six-minute walk distance at six-month follow-up. Secondary outcomes are Actigraph-measured physical activity, brachial artery flow-mediated dilation (FMD), gastrocnemius muscle biopsy measures of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, gastrocnemius muscle perfusion (measured by magnetic resonance imaging (MRI)) and gastrocnemius muscle characteristics (measured by muscle biopsy).

To achieve the specific aims, the study will randomize 190 participants age 55 and older with PAD to one of two groups: cocoa flavanols vs placebo. Participants will be followed for six months.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age 55 and older

  2. Presence of peripheral artery disease (PAD). PAD will be defined as either:

  3. An ABI <= 0.90 at baseline.

  4. Vascular lab evidence of PAD (such as a toe brachial pressure < 0.70 or anankle brachial index less than or equal to 0.90), or angiographic evidence ofPAD defined as at least 70% stenosis of an artery supplying the lowerextremities.

  5. An ABI of >0.90 and <=1.00 who experience a a 20% or greater drop in ABI ineither leg after the heel-rise test will also be included.

Exclusion

Exclusion Criteria:

  1. Above- or below-knee amputation

  2. Critical limb ischemia

  3. Wheelchair confinement or requiring a walker to ambulate

  4. Walking is limited by a symptom other than PAD

  5. Current foot ulcer on bottom of foot

  6. Failure to successfully complete the one-week study run-in

  7. Planned major surgery, coronary or leg revascularization during the next eightmonths

  8. Major surgery, coronary or leg revascularization or major cardiovascular event inthe previous three months

  9. Major medical illness including lung disease requiring oxygen, Parkinson's disease,a life-threatening illness with life expectancy less than eight months, or cancerrequiring treatment in the previous two years. [NOTE: potential participants maystill qualify if they have had treatment for an early stage cancer in the past twoyears and the prognosis is excellent. Participants who require oxygen only at nightmay still qualify.]

  10. Mini-Mental Status Examination (MMSE) score < 23

  11. Allergy to the study intervention

  12. Potential participants who have taken cocoa supplements in previous three months,are unwilling to avoid taking cocoa flavanol supplements, or are consuming darkchocolate regularly (i.e. approximately 1.5 ounces of dark chocolate more than threetimes per week, or more than 4.5 ounces per week).

  13. Non-English speaking

  14. Participation in or completion of a clinical trial in the previous three months. [NOTE: after completing a stem cell or gene therapy intervention, participants willbecome eligible after the final study follow-up visit of the stem cell or genetherapy study so long as at least six months have passed since the finalintervention administration. After completing a supplement or drug therapy (otherthan stem cell or gene therapy), participants will be eligible after the final studyfollow-up visit as long as at least three months have passed since the finalintervention of the trial.]

  15. Visual impairment that limits walking ability

  16. Six-minute walk distance of <500 feet or >1600 feet.

  17. Participation in a supervised treadmill exercise program in previous three months

  18. Unable to tolerate caffeine

  19. In addition to the above criteria, investigator discretion will be used to determineif the trial is unsafe or not a good fit for the potential participant

Study Design

Total Participants: 190
Treatment Group(s): 2
Primary Treatment: cocoa flavanols
Phase: 3
Study Start date:
November 19, 2021
Estimated Completion Date:
January 31, 2027

Connect with a study center

  • Northwestern University

    Chicago, Illinois 60611
    United States

    Active - Recruiting

  • University of Chicago

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • University of Minnesota

    Minneapolis, Minnesota 55455
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.