The COCOA-PAD II Trial

• Status: Recruiting
• Trial end date: 2026-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwestern University
• Collaborators: National Institute on Aging (NIA); University of Chicago; University of Minnesota

Criteria

Inclusion Criteria:

1. Age 55 and older

2. Presence of peripheral artery disease (PAD). PAD will be defined as either an ABI <= 0.90 at baseline or vascular lab evidence of PAD or angiographic evidence of PAD.

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 eight months

8. Major surgery, coronary or leg revascularization or major cardiovascular event in the 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 cancer requiring treatment in the previous two years. [NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may 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 dark chocolate at a frequency of once weekly or more

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 will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention 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 determine if the trial is unsafe or not a good fit for the potential participant