A Phase 3 interventional study of cocoa flavanols and placebo in Peripheral Artery Disease, sponsored by Northwestern University. Recruiting at 3 sites in United States. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2026-05-28.
Sponsored by Northwestern University · Phase 3, Interventional, and Treatment
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.
1,542 studies on the registry are indexed under Peripheral Arterial Disease; 282 are open to participants now.
This study's planned enrollment of 190 is above the median of 74 across 1,066 interventional studies indexed under Peripheral Arterial Disease.
Browse Peripheral Arterial Disease studies →Northwestern University is the lead sponsor of 1,396 studies on the registry; 199 are open to participants now.
Of its 102 completed or terminated interventional studies of FDA-regulated products, 73 (72%) have results posted.
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Presence of peripheral artery disease (PAD). PAD will be defined as either:
Exclusion Criteria:
Drug: cocoa flavanols
Drug: placebo
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.
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.
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-up
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-up
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-up
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-up
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-up
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.
Time frame: Baseline to six-month follow-up
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
Time frame: Six-month follow-up to 2- and 4-weeks post follow-up
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-up
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-up
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-up
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-up
Six-month change in gut microbial composition
The trial will determine whether cocoa flavanols, compared to placebo, favorably alter gut microbial composition at six-month follow-up.
Time frame: Baseline to six-month follow-up
Association of six-minute walk distance with six-month change in gut microbial composition
The trial will determine whether cocoa flavanol-induced changes in gut microbial composition, compared to placebo, between baseline and 6-month follow-up are associated with greater improvement in six-minute walk distance.
Time frame: Baseline to six-month follow-up
Association of calf perfusion with six-month change in gut microbial composition
The trial will determine whether cocoa flavanol-induced changes in gut microbial composition, compared to placebo, between baseline and 6-month follow-up are associated with greater improvement in calf perfusion.
Time frame: Baseline to six-month follow-up
Association of metabolomic profiles with improved six-minute walk distance.
The trial will perform microbe-associated metabolomic profiling in blood and stool at six-month follow-up to identify metabolomic profiles that are associated with improved six-minute walk distance at 6-month follow-up.
Time frame: Baseline to six-month follow-up
Association of metabolomic profiles with improved calf perfusion
The trial will perform microbe-associated metabolomic profiling in blood and stool at six-month follow-up to identify metabolomic profiles that are associated with improved calf perfusion at 6-month follow-up.
Time frame: Baseline to six-month follow-up
Association of metabolomic profiles with six-minute walk distance
The trial will perform microbe-associated metabolomic profiling in blood and stool at six-month follow-up to identify metabolomic profiles that are associated with improved six-minute walk distance at six-month follow-up.
Time frame: Baseline to six-month follow-up
Plan to share: No
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