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 下肢外周动脉疾病（PAD）是全身性动脉粥样硬化的表现， 全球超过2.36亿人。PAD患者的生活质量（QOL）低于其 健康的同行，部分原因是身体机能明显下降。非侵入性疗法很少 目前存在改善PAD患者的功能表现和恢复QOL的方法。的目标 建议的实验是确定家庭为基础的腿部热疗（HT）对下肢的好处 PAD患者的功能和QOL。这种新颖的方法包括定制工程裤子和一个 便携式水泵热水在裤子中循环，均匀地加热臀部、大腿和小腿。 该系统在家庭环境中使用安全、方便，无需监护。我们证明 使用这些定制的水循环裤反复暴露在腿部HT中可以增强肌肉力量， 以及在年轻久坐个体中肌肉损伤后的毛细血管化和加速恢复。中 在PAD的临床前模型中，我们报道了HT通过反复下半身浸泡在水浴中增强 骨骼肌质量和强度。我们的第一个随机假对照试验在32例有症状的 PAD显示，监督腿HT引起了临床上有意义的改善，感知身体 功能我们最近的R21赞助的试点研究表明，以家庭为基础的，无人监督的腿部HT是安全的， 症状性PAD患者耐受良好。基于这些广泛的初步数据，我们建议 在110例PAD患者中进行随机、双盲、假对照临床试验， 持续12周的每日居家腿部HT对功能能力和QOL的影响。患者随机分配至每天两次 腿部HT组（n=55）将被要求使用水循环裤每天应用治疗90 min 用加热到42ºC的水灌注。在假手术组（n=55）中，将33ºC的水循环通过 裤子主要研究结果是基线和12- 15分钟步行距离之间的变化。 周跟进。次要结果包括腿部力量和疲劳性的变化， 身体机能成套测验评分和感知QOL的变化。在目标#2中，我们将确定组织- HT影响肌肉力量和步行能力的水平机制。我们将评估骨骼 肌肉形态和血流使用磁共振成像（MRI）和活检从小腿 肌肉.如果基于我们初步数据的结论得到证实，那么拟议的实验将 提供了一个基于证据的可行性和有效性的框架，一种新的，直接的方法， 改善PAD患者的功能表现和生活质量。鉴于其可及性、耐受性和易用性， 使用，HT具有在临床环境中快速翻译和应用的潜力，从而打开新的 PAD的非侵入性管理的视野。 Bruno Roseguini博士