Peripheral Artery Disease
Conditions
Keywords
cocoa flavanols
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.
Interventions
DRUGcocoa 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.
DRUGplacebo
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.
Sponsors
Northwestern University
National Institute on Aging (NIA)
University of Minnesota
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 55 and older 2. Presence of peripheral artery disease (PAD). PAD will be defined as either: 1. An ABI \<= 0.90 at baseline. 2. 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. 3. 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.
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 regularly (i.e. approximately 1.5 ounces of dark chocolate more than three times per week, or more than 4.5 ounces per week). 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Six-month change in six-minute walk distance | 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
| Measure | Time frame | Description |
|---|---|---|
| Six-month change in gastrocnemius muscle perfusion (measured by magnetic resonance imaging (MRI)) | 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. |
| Six-month change in brachial artery flow-mediated dilation (FMD) | 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. |
| Six-month change in Actigraph-measured physical activity | 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. |
| Six-month change in calf muscle endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS | 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. |
| Six-month change in calf muscle characteristics (measured by calf muscle biopsy) | 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. |
| Six minute walk at two and four week follow-up after intervention completion. | 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 |
Countries
United States
Contacts
CONTACTMary McDermott, MD
CONTACTKathryn Domanchuk, BS
PRINCIPAL_INVESTIGATORMary McDermott, MD
Northwestern University
Outcome results
None listed