The COCOA-PAD II Trial
ConditionPeripheral Artery Disease
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age55+
SponsorNorthwestern University
About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 55 and older
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.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
cocoa flavanols
DrugThe 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
DrugThe 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.
Treatment groups
190 Participants
are divided into 2 treatment groupsGroup A: cocoa flavanolsActive comparator 1 intervention
Group B: placeboPlacebo comparator 1 intervention
Trial outcomes
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.
Time frame
Baseline to six-month follow-upSecondary outcomes
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.
Time frame
Baseline to six-month follow-up2
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.
Time frame
Baseline to six-month follow-up3
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.
Time frame
Baseline to six-month follow-up4
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.
Time frame
Baseline to six-month follow-upOther outcomes
1
Six-month change in plasma abundance of cocoa flavanols
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-up2
Association of calf perfusion with baseline gut microbial diversity with response to cocoa flavanols
The trial will determine whether baseline gut microbial diversity and composition are associated with the degree of response to cocoa flavanols, compared to placebo, measured by greater improvement calf perfusion at 6-month follow-up.
Time frame
Baseline to six-month follow-up3
Association of six-minute walk distance with baseline gut microbial diversity with response to cocoa flavanols
The trial will determine whether baseline gut microbial diversity and composition are associated with the degree of response to cocoa flavanols, compared to placebo, measured by greater improvement in six-minute walk distance at 6-month follow-up.
Time frame
Baseline to six-month follow-up4
Six-month change in gut microbial diversity
The trial will determine whether cocoa flavanols, compared to placebo, favorably alter gut microbial diversity at six-month follow-up.
Time frame
Baseline to six-month follow-upSponsors and contacts
Click on the lead sponsor to view all of their trials.
Northwestern University
Lead sponsor
National Institute on Aging (NIA)
Collaborator
University of Minnesota
Collaborator
University of Chicago
Collaborator
Source ClinicalTrials.gov