Trial Outcomes & Findings for Cocoa to Improve Walking Performance in Peripheral Artery Disease (NCT NCT02876887)
NCT ID: NCT02876887
Last Updated: 2020-08-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
44 participants
Primary outcome 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.
Results posted on
2020-08-06
Participant Flow
Participant milestones
| Measure |
Cocoa
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
21
|
|
Overall Study
COMPLETED
|
19
|
21
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cocoa to Improve Walking Performance in Peripheral Artery Disease
Baseline characteristics by cohort
| Measure |
Cocoa
n=23 Participants
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=21 Participants
Three servings per day of placebo beverages for six months.
Placebo
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
71 years
STANDARD_DEVIATION 7 • n=93 Participants
|
73 years
STANDARD_DEVIATION 7 • n=4 Participants
|
72 years
STANDARD_DEVIATION 7 • n=27 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
29 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
19 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
23 participants
n=93 Participants
|
21 participants
n=4 Participants
|
44 participants
n=27 Participants
|
PRIMARY outcome
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.Population: Nineteen and 21 study participants in the cocoa and placebo groups, respectively, completed the six-minute walk at both baseline and 6-month follow-up.
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.
Outcome measures
| Measure |
Cocoa
n=19 Participants
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=21 Participants
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Change From Baseline in Six-minute Walk Distance
Six-month, 2.5 hours after study beverage (meters)
|
18.4 meters
Interval 0.34 to 36.5
|
-24.2 meters
Interval -40.7 to -7.8
|
|
Change From Baseline in Six-minute Walk Distance
Six-month, 24 hours after study beverage (meters)
|
15.1 meters
Interval -1.9 to 32.1
|
-2.9 meters
Interval -19.4 to 13.6
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upPopulation: Eighteen and 19 study participants in the cocoa and placebo groups, respectively, participated in both the baseline and 6-month follow-up treadmill test.
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.
Outcome measures
| Measure |
Cocoa
n=18 Participants
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=19 Participants
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Change From Baseline in Maximal and Pain-free Treadmill Walking Time
Maximal treadmill minutes, 48 hrs post beverage
|
-0.03 minutes
Interval -1.16 to 1.1
|
0.28 minutes
Interval -0.79 to 1.34
|
|
Change From Baseline in Maximal and Pain-free Treadmill Walking Time
Pain-free treadmill minutes, 48 hrs post beverage
|
-0.07 minutes
Interval -1.13 to 1.0
|
0.39 minutes
Interval -0.64 to 1.43
|
SECONDARY outcome
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.Population: Fifteen and 17 study participants in the cocoa and placebo groups, respectively, participated in brachial artery flow-mediated dilation at baseline and 6-month follow-up.
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.
Outcome measures
| Measure |
Cocoa
n=15 Participants
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=17 Participants
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Change in Baseline From Brachial Artery Flow-mediated Dilation: Change in Brachial Artery Diameter
FMD change, 2.5 hours after study beverage
|
-0.65 Percent change
Interval -2.08 to 0.78
|
0.63 Percent change
Interval -0.69 to 1.96
|
|
Change in Baseline From Brachial Artery Flow-mediated Dilation: Change in Brachial Artery Diameter
FMD change, 24 hours after study beverage
|
0.04 Percent change
Interval -1.23 to 1.32
|
-0.59 Percent change
Interval -1.96 to 0.79
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upPopulation: Fifteen and 19 study participants in the cocoa and placebo groups, respectively, wore an ActiGraph accelerometer at baseline and 6-month follow-up.
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.
Outcome measures
| Measure |
Cocoa
n=15 Participants
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=19 Participants
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Change From Baseline Accelerometer-measured Physical Activity
|
-1919 activity counts
Interval -17743.0 to 13904.0
|
-8981 activity counts
Interval -22743.0 to 4780.0
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upPopulation: Ten and 6 study participants in the cocoa and placebo groups, respectively, completed muscle biopsy at baseline and 6-month follow-up.
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.
Outcome measures
| Measure |
Cocoa
n=10 Participants
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=6 Participants
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Change in Baseline Calf Skeletal Muscle Measures: Abundance of PGC1α, Myostatin and Follistatin
Abundance of PGC1α
|
0.09 Arbitrary units
Interval -0.09 to 0.28
|
0.04 Arbitrary units
Interval -0.21 to 0.29
|
|
Change in Baseline Calf Skeletal Muscle Measures: Abundance of PGC1α, Myostatin and Follistatin
Abundance of myostatin
|
0.26 Arbitrary units
Interval 0.05 to 0.47
|
0.15 Arbitrary units
Interval -0.14 to 0.43
|
|
Change in Baseline Calf Skeletal Muscle Measures: Abundance of PGC1α, Myostatin and Follistatin
Abundance of follistatin
|
-0.03 Arbitrary units
Interval -0.2 to 0.15
|
0.09 Arbitrary units
Interval -0.15 to 0.34
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upPopulation: Thirteen and 13 study participants in the cocoa and placebo groups, respectively, completed MRI testing at baseline and 6-month follow-up.
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.
Outcome measures
| Measure |
Cocoa
n=13 Participants
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=13 Participants
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Change in Baseline MRI-Measured Calf Skeletal Muscle Perfusion
|
0.10 ml/min/100 gram
Interval -0.25 to 0.45
|
-0.32 ml/min/100 gram
Interval -0.67 to 0.03
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upPopulation: Ten and 6 study participants in the cocoa and placebo groups, respectively, completed muscle biopsy at baseline and 6-month follow-up.
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.
Outcome measures
| Measure |
Cocoa
n=10 Participants
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=6 Participants
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Change in Baseline Calf Skeletal Muscle Measures: Citrate Synthase and COX Activity
Citrate synthase activity
|
-0.25 (nmol/min/mg protein)
Interval -3.85 to 3.36
|
-1.10 (nmol/min/mg protein)
Interval -5.98 to 3.77
|
|
Change in Baseline Calf Skeletal Muscle Measures: Citrate Synthase and COX Activity
COX activity
|
-4.6 (nmol/min/mg protein)
Interval -37.2 to 28.0
|
-90 (nmol/min/mg protein)
Interval -134.1 to -46.0
|
Adverse Events
Cocoa
Serious events: 7 serious events
Other events: 0 other events
Deaths: 1 deaths
Placebo
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cocoa
n=23 participants at risk
Three servings per day of epicatechin-rich (75 mg daily) cocoa beverages for six months.
Cocoa
|
Placebo
n=21 participants at risk
Three servings per day of placebo beverages for six months.
Placebo
|
|---|---|---|
|
Psychiatric disorders
Hospitalization for depression
|
4.3%
1/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
0.00%
0/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
|
Cardiac disorders
Death
|
4.3%
1/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
0.00%
0/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
|
Vascular disorders
Lower extremity revascularization
|
4.3%
1/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
0.00%
0/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
|
Skin and subcutaneous tissue disorders
Food ulcer with cellulitis
|
4.3%
1/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
0.00%
0/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
|
Renal and urinary disorders
Prostatic enlargement with associated symptoms
|
4.3%
1/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
0.00%
0/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
|
Vascular disorders
Other/unknown
|
4.3%
1/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
0.00%
0/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
4.8%
1/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
|
Vascular disorders
Ischemic stroke
|
4.3%
1/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
0.00%
0/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/23 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
4.8%
1/21 • Participants were formally asked once per month (1 mo, 2 mo, 3 mo, 4 mo, 5 mo, 6 mo) whether or not they had any hospitalizations.
The following categories were used to define serious adverse events- 1. Death 2. Cardiovascular events associated with hospitalization 3. Hospitalizations for operations or medical conditions other than cardiovascular events. 4. An untoward medical occurrence resulting in persistent or significant disability/incapacity. 5. Excessive weight gain in the amount of 20 pounds or more. Information regarding other adverse events was not collected.
|
Other adverse events
Adverse event data not reported
Additional Information
Mary McDermott, MD, Jeremiah Stamler Professor
Northwestern University
Phone: 1 312 503 6419
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place