The COCOA-PAD II Trial

NCT ID: NCT04794530

Last Updated: 2025-05-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-19
• Study Completion Date: 2027-01-31

Brief 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.

Conditions

Peripheral Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

cocoa flavanols

Group Type: ACTIVE_COMPARATOR

cocoa flavanols

Intervention Type: DRUG

The cocoa flavanols intervention is manufactured by Mars Inc. Participants randomized to cocoa flavanols will take two capsules daily of cocoa flavanols. The two capsules of cocoa flavanols will contain approximately 500 mg of cocoa flavanols and appoximately 80 mg of (-)-epicatechin.

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

The placebo intervention will be manufactured by Mars Inc. and will appear identical to the cocoa flavanols intervention. Participants will take two capsules daily of placebo. The placebo will be a cellulose based capsule and will not contain cocoa flavanols or (-)-epicatechin.

Interventions

cocoa flavanols

The cocoa flavanols intervention is manufactured by Mars Inc. Participants randomized to cocoa flavanols will take two capsules daily of cocoa flavanols. The two capsules of cocoa flavanols will contain approximately 500 mg of cocoa flavanols and appoximately 80 mg of (-)-epicatechin.

Intervention Type: DRUG

placebo

The placebo intervention will be manufactured by Mars Inc. and will appear identical to the cocoa flavanols intervention. Participants will take two capsules daily of placebo. The placebo will be a cellulose based capsule and will not contain cocoa flavanols or (-)-epicatechin.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 55 and older

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

1. An ABI <= 0.90 at baseline.

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

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

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 regularly (i.e. approximately 1.5 ounces of dark chocolate more than three times 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 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

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Mary McDermott

Jeremiah Stamler Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary McDermott, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Site Status: RECRUITING

University of Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mary McDermott, MD

Role: CONTACT

mdm608@northwestern.edu

312-503-6419

Kathryn Domanchuk, BS

Role: CONTACT

k-domanchuk@northwestern.edu

312-503-6438

Facility Contacts

Mary McDermott, MD

Role: primary

mdm608@northwestern.edu

312-503-6419

Tamar Polonsky, MD

Role: primary

tpolonsky@bsd.uchicago.edu

312-608-0250

Diane Treat-Jacobson, PhD

Role: primary

treat001@umn.edu

612-624-7613

Other Identifiers

R01AG068458-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU00213897

Identifier Type: -

Identifier Source: org_study_id