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

Primary Purpose

Peripheral Artery Disease

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
cocoa flavanols
placebo
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Artery Disease focused on measuring cocoa flavanols

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Northwestern UniversityRecruiting
  • University of ChicagoRecruiting
  • University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

cocoa flavanols

placebo

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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

Full Information

First Posted
March 7, 2021
Last Updated
May 22, 2023
Sponsor
Northwestern University
Collaborators
National Institute on Aging (NIA), University of Minnesota, University of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT04794530
Brief Title
The COCOA-PAD II Trial
Acronym
COCOA-PAD II
Official Title
COCOA Flavanols to Improve Walking Performance in PAD: the COCOA-PAD II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 19, 2021 (Actual)
Primary Completion Date
May 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwestern University
Collaborators
National Institute on Aging (NIA), University of Minnesota, University of Chicago

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Artery Disease
Keywords
cocoa flavanols

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
190 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
cocoa flavanols
Arm Type
Active Comparator
Arm Title
placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
cocoa flavanols
Intervention Description
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
Intervention Name(s)
placebo
Intervention Description
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 Measure Information:
Title
Six-month change in six-minute walk distance
Description
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.
Time Frame
Baseline to six-month follow-up
Secondary Outcome Measure Information:
Title
Six-month change in gastrocnemius muscle perfusion (measured by magnetic resonance imaging (MRI))
Description
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.
Time Frame
Baseline to six-month follow-up
Title
Six-month change in brachial artery flow-mediated dilation (FMD)
Description
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.
Time Frame
Baseline to six-month follow-up
Title
Six-month change in Actigraph-measured physical activity
Description
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.
Time Frame
Baseline to six-month follow-up
Title
Six-month change in calf muscle endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS
Description
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.
Time Frame
Baseline to six-month follow-up
Title
Six-month change in calf muscle characteristics (measured by calf muscle biopsy)
Description
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.
Time Frame
Baseline to six-month follow-up
Title
Six minute walk at two and four week follow-up after intervention completion.
Description
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
Time Frame
Six-month follow-up to 2- and 4-weeks post follow-up
Other Pre-specified Outcome Measures:
Title
Six-month change in plasma abundance of cocoa flavanols
Description
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
Time Frame
Baseline to six-month follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 55 and older 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: 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 at a frequency of once weekly or more 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mary McDermott, MD
Phone
312-503-6419
Email
mdm608@northwestern.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kathryn Domanchuk, BS
Phone
312-503-6438
Email
k-domanchuk@northwestern.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary McDermott, MD
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mary McDermott, MD
Phone
312-503-6419
Email
mdm608@northwestern.edu
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tamar Polonsky, MD
Phone
312-608-0250
Email
tpolonsky@bsd.uchicago.edu
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diane Treat-Jacobson, PhD
Phone
612-624-7613
Email
treat001@umn.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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The COCOA-PAD II Trial

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