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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG068458-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
| University of Minnesota | OTHER |
| University of Chicago | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| cocoa flavanols | Active Comparator |
| |
| placebo | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cocoa flavanols | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to six-month follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to six-month follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Inclusion Criteria:
Age 55 and older
Presence of peripheral artery disease (PAD). PAD will be defined as either:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mary McDermott, MD | Contact | 312-503-6419 | mdm608@northwestern.edu | |
| Kathryn Domanchuk, BS | Contact | 312-503-6438 | k-domanchuk@northwestern.edu |
| Name | Affiliation | Role |
|---|---|---|
| Mary McDermott, MD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University | Recruiting | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42035974 | Derived | 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 Apr 24;300:107450. doi: 10.1016/j.ahj.2026.107450. Online ahead of print. |
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| ID | Term |
|---|---|
| D058729 | Peripheral Arterial Disease |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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| placebo | Drug | 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 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. |
| 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. | 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. | 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. | 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 | Six-month follow-up to 2- and 4-weeks post follow-up |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline to six-month follow-up |
| University of Chicago | Recruiting | Chicago | Illinois | 60637 | United States |
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| University of Minnesota | Recruiting | Minneapolis | Minnesota | 55455 | United States |
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| D002318 |
| Cardiovascular Diseases |
| D016491 | Peripheral Vascular Diseases |