Leg heat therapy to improve functional performance in peripheral artery disease

腿部热疗可改善外周动脉疾病的功能表现

• 批准号: 10444199
• 负责人: Bruno T Roseguini
• 金额: $ 47.9万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444199
• 关键词: Activities of Daily Living; Address; Affect; American; Angiogenic Factor; Area; Atherosclerosis; Atrophic; Bathing; Biological; Biopsy; Biopsy Specimen; Blood; Blood capillaries; Blood flow; Buttocks; Cardiovascular system; Clinical; Controlled Clinical Trials; Coupled; Custom; Data; Diagnosis; Doctor of Philosophy; Double-Blind Method; Engineering; Equilibrium; Event; Exposure to; Fatty acid glycerol esters; Foundations; Goals; Heating; Home; Human; Immersion; Immunohistochemistry; Impairment; Individual; Infiltration; Intervention; Ischemia; Isotonic Exercise; Leg; Link; Lower Extremity; Magnetic Resonance Imaging; Modeling; Morphology; Muscle; Muscle Fatigue; Muscular Atrophy; Myalgia; National Institute on Aging; Outcome Study; Pain; Painless; Participant; Pathway interactions; Patients; Perceived quality of life; Performance; Peripheral arterial disease; Persons; Physical Function; Physical Performance; Pilot Projects; Pre-Clinical Model; Pump; Quality of life; Randomized; Randomized Clinical Trials; Recovery; Reporting; Research; Resistance; Safety; Skeletal Muscle; Supervision; System; Therapeutic; Therapeutic heat application; Thigh structure; Tissues; Translating; Translations; Walking; Water; Work; arterial spin labeling; base; clinical practice; combat; compliance behavior; diet-induced obesity; evidence base; exercise intolerance; exercise regimen; experimental study; follow-up; functional decline; functional disability; improved; meter; mortality; muscle form; muscle strength; novel; novel strategies; older patient; pilot trial; placebo group; portability; secondary outcome; sedentary; skeletal; tool; walking speed

PROJECT SUMMARY Lower-extremity peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis that affects more than 236 million individuals worldwide. Patients with PAD have a worse quality of life (QOL) than their healthy counterparts, due in part to the marked decline in physical functioning. Few non-invasive therapies currently exist to improve functional performance and restore QOL in people with PAD. The goal of the proposed experiments is to determine the benefits of home-based leg heat therapy (HT) on lower-extremity functioning and QOL in patients with PAD. This novel approach consists of custom engineered trousers and a portable water pump. Hot water is circulated through the trousers, evenly heating the buttocks, thighs and calf. This system is safe and convenient for application in the home setting without supervision. We demonstrated that repeated exposure to leg HT using these customized water-circulating trousers enhanced muscle strength and capillarization and accelerated recovery following muscle damage in young, sedentary individuals. In a preclinical model of PAD, we reported that HT via repeated lower-body immersion in a water bath enhanced skeletal muscle mass and strength. Our first randomized sham-controlled trial in 32 patients with symptomatic PAD revealed that supervised leg HT elicited a clinically meaningful improvement in perceived physical functioning. Our recent R21-sponsored pilot study revealed that home-based, unsupervised leg HT is safe and well-tolerated by symptomatic PAD patients. Building upon these extensive preliminary data, we propose to conduct a randomized, double-blind, sham-controlled clinical trial in 110 patients with PAD to establish the effect of daily home-based leg HT for 12 weeks on functional capacity and QOL. Patients randomized to the leg HT group (n=55) will be asked to apply the treatment daily for 90 min using water-circulating trousers perfused with water heated to 42ºC. In the sham group (n=55), water at 33ºC will be circulated through the trousers. The primary study outcome is the change in 6-minute walk distance between baseline and the 12- week follow up. Secondary outcomes include changes in leg strength and fatigability, changes in the short physical performance battery score and changes in perceived QOL. In Aim #2, we will determine the tissue- level mechanisms by which HT affects muscle strength and walking performance. We will assess skeletal muscle morphology and blood flow using magnetic resonance imaging (MRI) and biopsies from the calf muscle. If the conclusions based on our preliminary data are substantiated, the proposed experiments will provide an evidence-based framework of feasibility and efficacy of a novel, straightforward approach to improve functional performance and QOL in patients with PAD. Given its accessibility, tolerability and ease of use, HT has the potential for rapid translation and application in the clinical setting, thereby opening new horizons for the non-invasive management of PAD. Bruno Roseguini, Ph.D.

项目摘要 下部外周动脉疾病（PAD）是系统性动脉粥样硬化的表现，影响 全球超过2.36亿个人。 PAD患者的生活质量（QOL）比他们 健康对应物，部分原因是身体机能明显下降。很少有非侵入性疗法 目前存在以提高功能性能并恢复使用PAD的人的QOL。目标的目标 拟议的实验是确定基于家庭腿部热疗法（HT）对低超级性的好处 PAD患者的功能和QOL。这种新颖的方法包括定制工程裤子和 便携式水泵。热水通过裤子循环，甚至加热臀部，大腿和小腿。 该系统在不监督的情况下可以安全方便地在家庭环境中应用。我们证明了 使用这些定制的水循环裤可以重复接触腿HT，增强了肌肉力量 年轻人久坐的个体肌肉损害后，毛细管和加速恢复。在 PAD的临床前模型，我们报告了通过重复的低体浸入水浴中的HT增强 骨骼肌质量和力量。我们在32例有症状的患者中进行的首次随机假手术对照试验 垫子表明，有监督的腿HT引起了临床意义上有意义的感知身体的改善 功能。我们最近发起的R21试点研究表明，基于家庭的，无监督的腿部HT是安全的，并且 有症状的PAD患者耐受性良好。在这些广泛的初步数据的基础上，我们建议 在110例PAD患者中进行随机，双盲，假手术对照临床试验，以建立 每日家庭腿部HT在12周内对功能能力和生活质量的影响。随机分配给 腿HT组（n = 55）将每天使用水循环裤每天应用90分钟 用加热至42ºC的水灌注。在假手术组（n = 55）中，将通过33ºC的水通过 裤子。主要研究结果是基线和12-之间的6分钟步行距离的变化 周跟进。次要结果包括腿部强度和疲劳性的变化，短暂的变化 身体性能电池评分和感知到的生活质量的变化。在AIM＃2中，我们将确定组织 HT会影响肌肉力量和步行性能的水平机制。我们将评估骨骼 使用磁共振成像（MRI）和活检的肌肉形态和血流 肌肉。如果基于我们的初步数据的结论得到证实，则提出的实验将 提供一个基于证据的框架，以新颖，直接方法的可行性和效率 改善PAD患者的功能性能和QOL。鉴于其可访问性，容忍度和易用性 使用，HT有可能在临床环境中快速翻译和应用 无创管理的视野。 Bruno Roseguini博士