COCOA to improve walking performance in Peripheral Artery Disease: the COCOA-PAD Study

Project: Research project

Project Details

Description

Our work and that of others demonstrate that older men and women with lower extremity peripheral artery disease (PAD) have greater functional impairment and more rapid functional decline than older people without PAD. The functional impairments documented in older people with PAD are associated with mobility loss, increased mortality, and poor quality of life. Yet only two medications are FDA approved for improving the walking limitations associated with PAD.
Pre-clinical evidence shows that cocoa and its major flavanol component, epicatechin, have 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.
We propose a pilot study of 44 PAD participants age 65 and older: a double-blind, randomized controlled pilot clinical trial to provide preliminary data to address our 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 our primary aim, we 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 our secondary aims, we will determine whether PAD participants randomized to cocoa have improved treadmill walking performance, improved brachial artery flow-mediated dilation, and favorable changes in calf muscle biopsy measures of mitochondrial function, mitochondrial biogenesis, follistatin, myostatin, and capillary density. Our outcome measures will be carefully timed relative to the last intervention dose to distinguish between the acute vs. chronic effects of cocoa-epicatechin.
If our 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.
StatusFinished
Effective start/end date6/15/162/28/19

Funding

  • National Institute on Aging (5R21AG050897-02)

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