Clinical trial NCT02876887: Cocoa to Improve Walking Performance in Peripheral Artery Disease
Official title: Cocoa to Improve Walking Performance in Peripheral Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peripheral Artery Disease
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2016-08-24
Enrollment: 44
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The COCOA-PAD trial will determine whether epicatechin-rich cocoa daily for six months improves walking performance in individuals with peripheral artery disease compared to placebo.

Detailed description: Therapeutic properties that target pathophysiologic impairments in PAD. These therapeutic properties include improved skeletal muscle mitochondrial function, increased skeletal muscle capillary density, and favorable changes in skeletal muscle levels of myostatin and follistatin that increase muscle mass and strength. Cocoa also protects against ischemia-reperfusion injury, improves endothelial function, and reduces oxidative stress. In summary, epicatechin-rich cocoa targets and reverses several pathophysiologic processes that are common in PAD and that are associated with functional impairment and functional decline in PAD. However, the effect of chronic daily cocoa consumption on functional decline has not been studied in older people with PAD.

The COCOA-PAD trial is a pilot study of 44 PAD participants age 60 and older: a double-blind, randomized controlled pilot clinical trial to provide preliminary data to address the hypothesis that chronic daily epicatechin-rich cocoa improves lower extremity functioning in older people with PAD by improving mitochondrial oxidative metabolism, increasing calf muscle capillary density, promoting calf skeletal muscle mitochondrial biogenesis, and improving endothelial function.

In the primary aim, the investigators will determine whether PAD participants randomized to an epicatechin-rich cocoa beverage have greater increases or smaller declines in six-minute walk performance at 6-month follow-up, compared to those randomized to an identical appearing placebo drink with comparable caloric composition. In the secondary aims, the investigators will determine whether PAD participants randomized to cocoa have improved treadmill walking performance, improved brachial artery flow-mediated dilation, favorable changes in calf muscle biopsy measures of mitochondrial function, mitochondrial biogenesis, follistatin, myostatin, and capillary density, increased calf skeletal muscle regeneration and reduced oxidative stress, and increased MRI-measured calf muscle perfusion. Outcome measures will be carefully timed relative to the last intervention dose to distinguish between the acute vs. chronic effects of cocoa-epicatechin.

If the hypotheses are correct, results will be used to design a large, definitive randomized controlled trial of epicatechin-rich cocoa to improve lower extremity functioning and prevent mobility loss in the large and growing number of older people who are disabled by PAD.

Eligibility criteria: Inclusion Criteria:

1. All participants will be age 60 and older.
2. All participants will have PAD. PAD will be defined as follows. First, an ABI \< 0.90 at baseline is an inclusion criterion for PAD. Second, potential participants with an ABI \> 0.90 who have vascular lab evidence of PAD or angiographic evidence of PAD will be eligible.

Exclusion Criteria:

1. Above- or below-knee amputation.
2. Critical limb ischemia.
3. Wheelchair-bound or requiring a cane or walker to ambulate.
4. Walking is limited by a symptom other than PAD.
5. Baseline six-minute walk value of \<500 feet or \>1,600 feet
6. Lower extremity revascularization, major orthopedic surgery, cardiovascular event, or coronary revascularization in the previous three months.
7. Planned revascularization or major surgery during the next six months.
8. Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
9. Mini-Mental Status Examination (MMSE) score \< 23 or dementia.
10. Unwilling to attend three visits in one week for final outcome measures.
11. Allergy to chocolate.
12. Unwilling or unable to consume products manufactured on the same equipment that processes peanuts, tree nuts, egg, wheat, soy, and milk.
13. Use of cocoa-containing dietary supplements.
14. Unwilling to give up major dietary sources of epicatechin during the study.
15. Symptoms of heart failure or angina that limit walking activity more than ischemic leg symptoms, increase in angina, or angia at rest (i.e. unstable angina).
16. Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\]
17. Non-English speaking, a visual impairment that limits walking ability.
18. 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.

Primary outcomes:
measure: Change From Baseline in Six-minute Walk Distance
timeFrame: Change from baseline to six-month follow-up. Note - There will be two measures: One 2-3 hours after the final study beverage dose and one 24 hours after the final dose.
Secondary outcomes:
measure: Change From Baseline in Maximal and Pain-free Treadmill Walking Time
timeFrame: Change from baseline to six-month follow-up
measure: Change in Baseline From Brachial Artery Flow-mediated Dilation: Change in Brachial Artery Diameter
timeFrame: Change from baseline to six-month follow-up. Note - there will be two measures: One 2-3 hours after the final study beverage dose and one 24 hours after the final study beverage dose.
measure: Change From Baseline Accelerometer-measured Physical Activity
timeFrame: Change from baseline to six-month follow-up
measure: Change in Baseline Calf Skeletal Muscle Measures: Abundance of PGC1α, Myostatin and Follistatin
timeFrame: Change from baseline to six-month follow-up
measure: Change in Baseline MRI-Measured Calf Skeletal Muscle Perfusion
timeFrame: Change from baseline to six-month follow-up
measure: Change in Baseline Calf Skeletal Muscle Measures: Citrate Synthase and COX Activity
timeFrame: Change from baseline to six-month follow-up
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
Study officials:
affiliation: Northwestern University
name: Mary McDermott, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McDermott MM, Criqui MH, Domanchuk K, Ferrucci L, Guralnik JM, Kibbe MR, Kosmac K, Kramer CM, Leeuwenburgh C, Li L, Lloyd-Jones D, Peterson CA, Polonsky TS, Stein JH, Sufit R, Van Horn L, Villarreal F, Zhang D, Zhao L, Tian L. Cocoa to Improve Walking Performance in Older People With Peripheral Artery Disease: The COCOA-PAD Pilot Randomized Clinical Trial. Circ Res. 2020 Feb 28;126(5):589-599. doi: 10.1161/CIRCRESAHA.119.315600. Epub 2020 Feb 14.