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

可可改善外周动脉疾病患者的步行能力：COCOA-PAD 研究

• 批准号: 9295937
• 负责人: Mary McGrae McDermott
• 金额: $ 23.45万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9295937
• 关键词: Accelerometer; Acute; Address; Age; Appearance; Beverages; Biogenesis; Biopsy; Blood capillaries; Cell Respiration; Chocolate; Chronic; Citrate (si)-Synthase; Clinical Trials; Cocoa Powder; Consumption; Crista ampullaris; Cross-Over Trials; Darkness; Data; Differentiation and Growth; Disabled Persons; Dose; Double-Blind Method; FDA approved; Flavanol; Follistatin; GDF8 gene; Growth; Hand Strength; Health Care Costs; Heart failure; Hour; Human; Impairment; Ingestion; Intervention; Intervention Studies; Lower Extremity; Measures; Mediating; Medical; Mitochondria; Muscle; Muscular Atrophy; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome Measure; Oxidative Stress; Pain-Free; Participant; Patients; Performance; Perfusion; Peripheral arterial disease; Peroxisome Proliferation; Pharmaceutical Preparations; Physical activity; Pilot Projects; Placebos; Process; Property; Quality of life; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Reperfusion Injury; Skeletal Muscle; Taste Perception; Testing; Therapeutic; Time; Walking; Work; angiogenesis; brachial artery; capillary; cytochrome c oxidase; density; design; epicatechin; follow-up; functional decline; functional disability; improved; improved functioning; mortality; muscle form; muscle strength; older men; older women; pre-clinical; prevent; primary outcome; public health relevance; randomized trial; receptor; secondary outcome; transcription factor; treadmill

 DESCRIPTION (provided by applicant): 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. Ou 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.

 描述（由申请人提供）：我们和其他人的工作表明，患有下肢外周动脉疾病 (PAD) 的老年男性和女性比没有患下肢外周动脉疾病 (PAD) 的老年人有更严重的功能障碍和更快的功能衰退。外周动脉疾病 (PAD) 会导致行动能力丧失、死亡率增加和生活质量下降，但临床前证据表明，可可及其主要黄烷醇成分表儿茶素具有改善外周动脉疾病 (PAD) 相关步行限制的药物。针对 PAD 病理生理损伤的治疗特性 这些治疗特性包括改善骨骼肌线粒体功能、增加骨骼肌毛细血管密度以及骨骼肌肌生长抑制素和卵泡抑素水平的有利变化，从而增加肌肉质量和强度。总之，富含表儿茶素的可可针对并逆转多种病理生理过程。这种现象在 PAD 中很常见，并且与 PAD 的功能障碍和功能衰退有关。然而，我们尚未在患有 PAD 的老年人中研究长期每日可可摄入量对功能衰退的影响。我们建议对 44 名 65 岁的 PAD 参与者进行一项试点研究。及老年人：一项双盲、随机对照试点临床试验，旨在提供初步数据来验证我们的假设，即长期每日饮用富含表儿茶素的可可可通过改善线粒体氧化代谢、增加小腿肌肉来改善患有 PAD 的老年人的下肢功能毛细血管密度、促进小腿骨骼肌线粒体生物发生以及改善内皮功能 在我们的主要目标中，我们将确定随机饮用富含表儿茶素的可可饮料的 PAD 参与者在 6 个月时的六分钟步行表现是否有较大的提高或较小的下降。在我们的次要目标中，我们将确定随机饮用可可的 PAD 参与者是否改善了跑步机行走表现，改善了肱动脉。血流介导的扩张，以及小腿肌肉活检测量线粒体功能、线粒体生物发生、卵泡抑素、肌肉生长抑制素和毛细血管密度的有利变化，将相对于最后的干预剂量仔细计时，以区分急性与慢性影响。如果我们的假设正确，结果将用于设计富含表儿茶素的可可的大型、明确的随机对照试验，以改善下肢功能并防止大量且不断增加的老年人的活动能力丧失。因 PAD 致残的人。