The COCOA-PAD II Trial

NCT04794530 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: STU00213897R01AG068458-01A1
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 3

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

Keywords

cocoa flavanols

Outcome Measures

Primary Outcomes (1)

• Six-month change in six-minute walk distance

  Change in six-minute walk distance at six-month follow-up will be compared between those randomized to cocoa flavanols vs. those randomized to placebo.

  Baseline to six-month follow-up

Secondary Outcomes (6)

• Six-month change in gastrocnemius muscle perfusion (measured by magnetic resonance imaging (MRI))

  Baseline to six-month follow-up

• Six-month change in brachial artery flow-mediated dilation (FMD)

  Baseline to six-month follow-up

• Six-month change in Actigraph-measured physical activity

  Baseline to six-month follow-up

• Six-month change in calf muscle endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS

  Baseline to six-month follow-up

• Six-month change in calf muscle characteristics (measured by calf muscle biopsy)

  Baseline to six-month follow-up

Other Outcomes (10)

• Six-month change in plasma abundance of cocoa flavanols

  Baseline to six-month follow-up

• Association of calf perfusion with baseline gut microbial diversity with response to cocoa flavanols

  Baseline to six-month follow-up

• Association of six-minute walk distance with baseline gut microbial diversity with response to cocoa flavanols

  Baseline to six-month follow-up

Study Arms (2)

cocoa flavanols

ACTIVE COMPARATOR

Drug: cocoa flavanols

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

cocoa flavanols 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.

cocoa flavanols

placebo 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.

placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55 and older
• Presence of peripheral artery disease (PAD). PAD will be defined as either:
• An ABI \<= 0.90 at baseline.
• 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.
• 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.

You may not qualify if:

• Above- or below-knee amputation
• Critical limb ischemia
• Wheelchair confinement or requiring a walker to ambulate
• Walking is limited by a symptom other than PAD
• Current foot ulcer on bottom of foot
• Failure to successfully complete the one-week study run-in
• Planned major surgery, coronary or leg revascularization during the next eight months
• Major surgery, coronary or leg revascularization or major cardiovascular event in the previous three months
• 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. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
• Mini-Mental Status Examination (MMSE) score \< 23
• Allergy to the study intervention
• 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).
• Non-English speaking
• Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\]
• Visual impairment that limits walking ability

Sponsors & Collaborators

• Northwestern University: lead
• National Institute on Aging (NIA): collaborator
• University of Minnesota: collaborator
• University of Chicago: collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Study Officials

• Mary McDermott, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary McDermott, MD

CONTACT

312-503-6419; mdm608@northwestern.edu

Kathryn Domanchuk, BS

CONTACT

312-503-6438; k-domanchuk@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jeremiah Stamler Professor of Medicine

Study Record Dates

• First Submitted: March 7, 2021
• First Posted: March 12, 2021
• Study Start: November 19, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)