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The COCOA-PAD II Trial (COCOA-PAD II)

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ClinicalTrials.gov Identifier: NCT04794530
Recruitment Status : Recruiting
First Posted : March 12, 2021
Last Update Posted : June 21, 2022
Sponsor:
Collaborators:
National Institute on Aging (NIA)
University of Minnesota
University of Chicago
Information provided by (Responsible Party):
Mary McDermott, Northwestern University

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.


Condition or disease Intervention/treatment Phase
Peripheral Artery Disease Drug: cocoa flavanols Drug: placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 190 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: COCOA Flavanols to Improve Walking Performance in PAD: the COCOA-PAD II Trial
Actual Study Start Date : November 19, 2021
Estimated Primary Completion Date : May 31, 2026
Estimated Study Completion Date : December 31, 2026

Arm Intervention/treatment
Active Comparator: cocoa flavanols Drug: 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.

Placebo Comparator: placebo 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.




Primary Outcome Measures :
  1. Six-month change in six-minute walk distance [ Time Frame: Baseline to six-month follow-up ]
    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.


Secondary Outcome Measures :
  1. Six-month change in gastrocnemius muscle perfusion (measured by magnetic resonance imaging (MRI)) [ Time Frame: Baseline to six-month follow-up ]
    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.

  2. Six-month change in brachial artery flow-mediated dilation (FMD) [ Time Frame: Baseline to six-month follow-up ]
    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.

  3. Six-month change in Actigraph-measured physical activity [ Time Frame: Baseline to six-month follow-up ]
    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.

  4. Six-month change in calf muscle endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS [ Time Frame: Baseline to six-month follow-up ]
    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.

  5. Six-month change in calf muscle characteristics (measured by calf muscle biopsy) [ Time Frame: Baseline to six-month follow-up ]
    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.

  6. Six minute walk at two and four week follow-up after intervention completion. [ Time Frame: Six-month follow-up to 2- and 4-weeks post follow-up ]
    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


Other Outcome Measures:
  1. Six-month change in plasma abundance of cocoa flavanols [ Time Frame: Baseline to six-month follow-up ]
    The trial will determine whether lower plasma abundance of cocoa flavanols at baseline and whether greater increases in plasma abundance of cocoa flavanols at 6-month follow-up are associated with greater improvement in six-minute walk distance at 6-month follow-up, compared to higher plasma abundance of cocoa flavanols at baseline and compared to smaller increases in plasma cocoa flavanols at 6-month follow-up, respectively



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04794530


Contacts
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Contact: Mary McDermott, MD 312-503-6419 mdm608@northwestern.edu
Contact: Kathryn Domanchuk, BS 312-503-6438 k-domanchuk@northwestern.edu

Locations
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United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Mary McDermott, MD    312-503-6419    mdm608@northwestern.edu   
Sponsors and Collaborators
Northwestern University
National Institute on Aging (NIA)
University of Minnesota
University of Chicago
Investigators
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Principal Investigator: Mary McDermott, MD Northwestern University
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Responsible Party: Mary McDermott, Jeremiah Stamler Professor of Medicine, Northwestern University
ClinicalTrials.gov Identifier: NCT04794530    
Other Study ID Numbers: STU00213897
R01AG068458-01A1 ( U.S. NIH Grant/Contract )
First Posted: March 12, 2021    Key Record Dates
Last Update Posted: June 21, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mary McDermott, Northwestern University:
cocoa flavanols
Additional relevant MeSH terms:
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Peripheral Arterial Disease
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Peripheral Vascular Diseases