Peripheral Artery DiseaseCOCOA-PADNCT02876887
Cocoa to Improve Walking Performance in Peripheral Artery Disease
A study testing Cocoa in people with Peripheral Artery Disease, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Peripheral Artery Disease
- What is being tested?
- Cocoa
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to 15 Oct 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All participants will be age 60 and older.
- 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.
Who cannot join
- Above- or below-knee amputation.
- Critical limb ischemia.
- Wheelchair-bound or requiring a cane or walker to ambulate.
- Walking is limited by a symptom other than PAD.
- Baseline six-minute walk value of <500 feet or >1,600 feet
- Lower extremity revascularization, major orthopedic surgery, cardiovascular event, or coronary revascularization in the previous three months.
Show all 18Show fewer
- Planned revascularization or major surgery during the next six months.
- 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.]
- Mini-Mental Status Examination (MMSE) score < 23 or dementia.
- Unwilling to attend three visits in one week for final outcome measures.
- Allergy to chocolate.
- Unwilling or unable to consume products manufactured on the same equipment that processes peanuts, tree nuts, egg, wheat, soy, and milk.
- Use of cocoa-containing dietary supplements.
- Unwilling to give up major dietary sources of epicatechin during the study.
- 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).
- 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.]
- Non-English speaking, a visual impairment that limits walking ability.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
About this study
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.
Read the 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.
- Conditions
- Peripheral Artery Disease
- Being tested
- Cocoa, Placebo
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CocoaDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Cocoa | Active comparator | Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months. Receives: Drug: Cocoa |
| Placebo | Placebo comparator | Three servings per day of placebo beverages for six months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Six-minute Walk Distance
Following a standardized protocol, participants walked up and down a 100-ft hallway for 6 minutes after instruction to cover as much distance as possible.
Measured: 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 (6)
Change From Baseline in Maximal and Pain-free Treadmill Walking Time
Maximal treadmill walking time and time to ischemic leg symptom onset were measured using the Gardner-Skinner protocol at baseline and 6-month follow-up.
Measured: Change from baseline to six-month follow-up
Change in Baseline From Brachial Artery Flow-mediated Dilation: Change in Brachial Artery Diameter
Brachial artery flow-mediated dilation was measured in the proximal brachial artery (B mode and Doppler) after a 12-hour fast by Registered Diagnostic Cardiac Sonographers using a linear array vascular ultrasound transducer (Sequoia Model #256; frequency, 8 MHz; range, 5-8 MHz; Siemens Medical Solutions). A cuff proximal to the visualized brachial artery segment was inflated for 4 minutes at 50 mmHg above systolic pressure. Brachial artery images were obtained 60 seconds after cuff deflation and interpreted by a single reader, blinded to group assignment, at the University of Wisconsin Atherosclerosis Imaging Research Program Core Laboratory. Change in brachial artery diameter will be reported in percent change.
Measured: 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.
Change From Baseline Accelerometer-measured Physical Activity
Free-living physical activity was acquired over 7 days with the ActiGraph accelerometer. The accelerometer was worn on the right hip and removed only for bathing or sleeping.
Measured: Change from baseline to six-month follow-up
Change in Baseline Calf Skeletal Muscle Measures: Abundance of PGC1α, Myostatin and Follistatin
An open-muscle biopsy at baseline was performed in the medial head of the gastrocnemius muscle. Anesthesia was achieved with subcutaneous lidocaine. Subcutaneous tissue was dissected, and ≈250 mg of muscle was removed and immediately prepared for freezing at -80°C. At 6-month follow-up, the biopsy was repeated, adjacent to the original biopsy, identifiable by the scar.
Measured: Change from baseline to six-month follow-up
Change in Baseline MRI-Measured Calf Skeletal Muscle Perfusion
Arterial spin labeling with cardiovascular magnetic resonance imaging was used to measure changes in calf perfusion at 3 T between PAD participants receiving cocoa versus placebo. A thigh cuff was inflated to 250 mm Hg in the leg with the lowest ABI and rapidly deflated after 5 minutes. Seven control-tagged image pairs were acquired over 60 seconds using pulsed arterial spin labeling pulse sequence with single-shot echo-planar imaging readouts ( eld of view, 200×200 mm; matrix, 64×64; repetition time, 4000 ms; echo time, 32 ms; slice thickness, 10 mm). Perfusion was measured and quantified on a Siemens Healthcare workstation by coinvestigator C.M.K.
Measured: Change from baseline to six-month follow-up
Change in Baseline Calf Skeletal Muscle Measures: Citrate Synthase and COX Activity
An open-muscle biopsy at baseline was performed in the medial head of the gastrocnemius muscle. Anesthesia was achieved with subcutaneous lidocaine. Subcutaneous tissue was dissected, and ≈250 mg of muscle was removed and immediately prepared for freezing at -80°C. At 6-month follow-up, the biopsy was repeated, adjacent to the original biopsy, identifiable by the scar.
Measured: Change from baseline to six-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2016 (estimated)
- Study startJan 2017
- Primary completion15 Oct 2019
- Study completion15 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Mary McDermott, Northwestern University
- Investigators
- Mary McDermott, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02876887
- Sponsor's protocol ID
- STU00202741
- Other IDs
- R21AG050897
- Acronym
- COCOA-PAD
- Status last verified
- Jul 2020
- First submitted
- 16 May 2016
- Last updated
- 6 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 32078436
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cocoa to Improve Walking Performance in Peripheral Artery Disease
- ClinicalTrials.gov ID
- NCT02876887
- Acronym / sponsor ID
- COCOA-PAD / STU00202741
- Conditions
- Peripheral Artery Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Jan 2017 (actual)
- Primary completion
- 15 Oct 2019 (actual)
- Study completion
- 15 Oct 2019 (actual)
- First posted
- 24 Aug 2016 (estimated)
- Results
- Posted 6 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cocoa | Active comparator | Drug: CocoaThree servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months. |
| Placebo | Placebo comparator | Drug: PlaceboThree servings per day of placebo beverages for six months. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- All participants will be age 60 and older.
- 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.
Key exclusion criteria (18 listed)
- Above- or below-knee amputation.
- Critical limb ischemia.
- Wheelchair-bound or requiring a cane or walker to ambulate.
- Walking is limited by a symptom other than PAD.
- Baseline six-minute walk value of <500 feet or >1,600 feet
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cocoa | Drug | Cocoa |
| Placebo | Drug | Placebo |
Primary outcome
Change From Baseline in Six-minute Walk Distance
Time frame: 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.
Following a standardized protocol, participants walked up and down a 100-ft hallway for 6 minutes after instruction to cover as much distance as possible.
6 secondary outcomes
Change From Baseline in Maximal and Pain-free Treadmill Walking Time
Time frame: Change from baseline to six-month follow-up
Change in Baseline From Brachial Artery Flow-mediated Dilation: Change in Brachial Artery Diameter
Time frame: 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.
Change From Baseline Accelerometer-measured Physical Activity
Time frame: Change from baseline to six-month follow-up
Change in Baseline Calf Skeletal Muscle Measures: Abundance of PGC1α, Myostatin and Follistatin
Time frame: Change from baseline to six-month follow-up
Change in Baseline MRI-Measured Calf Skeletal Muscle Perfusion
Time frame: Change from baseline to six-month follow-up
Change in Baseline Calf Skeletal Muscle Measures: Citrate Synthase and COX Activity
Time frame: Change from baseline to six-month follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32078436McDermott 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary McDermott, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cocoa in people with Peripheral Artery Disease, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Six-minute Walk Distance (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02876887, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2020.