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Peripheral Artery DiseasePhase 3COCOA-PAD IINCT04794530

The COCOA-PAD II Trial

A Phase 3 study testing cocoa flavanols in people with Peripheral Artery Disease, run by Northwestern University at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 55 years and older
Conditions the study is for
Peripheral Artery Disease
What is being tested?
cocoa flavanols
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
190 participants
Where
3 sitesUnited States
Study dates
19 Nov 2021to 1 Jun 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 19Show fewer
  • 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
  • Six-minute walk distance of <500 feet or >1600 feet.
  • Participation in a supervised treadmill exercise program in previous three months
  • Unable to tolerate caffeine
  • 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

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Mary McDermott, MD contact

312-503-6419

mdm608@northwestern.edu

Kathryn Domanchuk, BS contact

312-503-6438

k-domanchuk@northwestern.edu

United States3 sites, 3 recruiting

  • Northwestern University

    Chicago, Illinois, 60611

    Mary McDermott, MD, 312-503-6419, mdm608@northwestern.edu

    Recruiting

  • University of Chicago

    Chicago, Illinois, 60637

    Tamar Polonsky, MD, 312-608-0250, tpolonsky@bsd.uchicago.edu

    Recruiting

  • University of Minnesota

    Minneapolis, Minnesota, 55455

    Diane Treat-Jacobson, PhD, 612-624-7613, treat001@umn.edu

    Recruiting

Other trials in United States

About this study

Official title: COCOA Flavanols to Improve Walking Performance in PAD: the COCOA-PAD II Trial

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.

Being tested
cocoa flavanols, placebo
Keywords
cocoa flavanols
Medical subject headings
Peripheral Arterial Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cocoa flavanolsDrug

    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.

  • placeboDrug

    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.

Study groups in NCT04794530
Study groupRoleWhat they receive
cocoa flavanolsActive comparatorNot described
Receives: Drug: cocoa flavanols
placeboPlacebo comparatorNot described
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to six-month follow-up

Secondary outcomes (6)

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

    Change in gastrocnemius muscle perfusion (measured by MRI) at six-month follow-up will be compared between those randomized to cocoa flavanols vs. those randomized to placebo.

    Measured: Baseline to six-month follow-up

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

    Change in brachial artery flow-mediated dilation (FMD) at six-month follow-up will be compared between those randomized to cocoa flavanols vs. those randomized to placebo.

    Measured: Baseline to six-month follow-up

  3. Six-month change in Actigraph-measured physical activity

    Change in Actigraph-measured physical activity at six-month follow-up will be compared between those randomized to cocoa flavanols vs. those randomized to placebo.

    Measured: Baseline to six-month follow-up

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

    Change in calf muscle biopsy measures of eNOS and phosphorylated eNOS at six-month follow-up will be compared between those randomized to cocoa flavanols vs. those randomized to placebo.

    Measured: Baseline to six-month follow-up

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

    Change in calf muscle characteristics (measured by calf muscle biopsy) at six-month follow-up will be compared between those randomized to cocoa flavanols vs. those randomized to placebo.

    Measured: Baseline to six-month follow-up

  6. Six minute walk at two and four week follow-up after intervention completion.

    The trial will determine whether cocoa flavanols, compared to placebo, have a persistent effect on improved six-minute walk distance at two weeks and four weeks after the study intervention is completed

    Measured: Six-month follow-up to 2- and 4-weeks post follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2021
  2. Study start19 Nov 2021
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion1 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
190 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04794530
Sponsor's protocol ID
STU00213897
Other IDs
R01AG068458-01A1
Acronym
COCOA-PAD II
Status last verified
May 2026
First submitted
7 Mar 2021
Last updated
28 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • McDermott MM, Cetlin MD, Domanchuk KJ, Xu S, Whipple MO, Polonsky T, Criqui MH, Guralnik JM, Tian L, Zhao L, Ho KJ, Greenland P, Treat-Jacobson D. Community-based recruitment with ankle brachial index testing to identify peripheral artery disease participants for randomized clinical trials. Am Heart J. 2026 Oct;300:107450. doi: 10.1016/j.ahj.2026.107450. Epub 2026 Apr 24.

    PubMed 42035974

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cocoa flavanols in people with Peripheral Artery Disease, run by Northwestern University at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Mary McDermott, MD (312-503-6419, mdm608@northwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Six-month change in six-minute walk distance (time frame: Baseline to six-month follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04794530, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.

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