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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要下肢外周动脉疾病（PAD）是全身性动脉粥样硬化的一种表现，影响全球有超过 2.36 亿 PAD 患者的生活质量 (QOL) 低于实际水平。健康盟友，部分原因是身体机能明显下降。目前存在的目标是改善 PAD 患者的功能表现并恢复 QOL。拟议的实验旨在确定家庭腿部热疗 (HT) 对下肢的益处这种新颖的方法包括定制设计的裤子和裤子。便携式水泵，热水通过裤子循环，均匀加热臀部、大腿和小腿。我们演示了该系统在家庭环境中的应用安全且方便，无需监督。使用这些定制的水循环裤反复暴露于腿部 HT 可以增强肌肉力量年轻、久坐的人肌肉损伤后的毛细血管化和加速恢复。在 PAD 的临床前模型中，我们报道了通过反复将下半身浸入水浴中来增强 HT 我们对 32 名有症状患者进行的第一项随机假对照试验。 PAD 表明，腿部 HT 可以在监督下，在感知身体方面带来具有临床意义的改善。我们最近由 R21 赞助的试点研究表明，在家进行、无人监督的腿部 HT 是安全且有效的。有症状的 PAD 患者耐受性良好。根据这些初步数据，我们建议对 110 名 PAD 患者进行了一项随机、双盲、假对照临床试验，以确定每日家庭腿部 HT 持续 12 周对随机分配至对照组的患者的功能能力和生活质量的影响。腿部 HT 组 (n=55) 将被要求每天使用水循环裤进行治疗 90 分钟在假手术组（n = 55）中，通过加热至 42°C 的水进行灌注，将检查 33°C 的水。主要研究结果是基线与 12 分钟步行距离之间的变化。次要结果包括腿部力量和疲劳度的变化以及短距离的变化。身体表现电池评分和感知生活质量的变化在目标#2中，我们将确定组织- HT 影响肌肉力量和行走表现的水平机制我们将评估骨骼。使用磁共振成像 (MRI) 和小腿活检进行肌肉形态和血流分析如果基于我们初步数据的结论得到证实，所提出的实验将得到证实。提供一个基于证据的框架，说明一种新颖、直接的方法的可行性和有效性鉴于其可及性、耐受性和易用性，可改善 PAD 患者的功能表现和生活质量。使用，HT具有在临床环境中快速转化和应用的潜力，从而开辟新的领域 PAD 非侵入性管理的前景。布鲁诺·罗斯吉尼博士