Leg heat therapy to improve functional performance in peripheral artery disease

项目总结 下肢外周动脉疾病(PAD)是系统性动脉粥样硬化的一种表现，影响 全球超过2.36亿人。PAD患者的生活质量(QOL)比他们的 健康的对应者，部分原因是身体功能明显下降。很少有非侵入性治疗 目前存在改善PAD患者的功能表现和恢复生活质量的方法。的目标是 拟议的实验是为了确定家庭腿部热疗(HT)对下肢的好处 PAD患者的功能和生活质量。这一新的方法包括定制工程裤子和一个 便携式水泵。热水通过裤子循环，均匀加热臀部、大腿和小腿。 该系统安全、方便，可在无人值守的家庭环境中使用。我们演示了 使用定制的循环水裤子反复暴露在腿部超负荷运动中，可以增强肌肉力量 在年轻人久坐不动的肌肉损伤后，毛细血管形成和加速恢复。在一个 PAD的临床前模型，我们报告了通过反复下半身浸泡在水浴中增强的HT 骨骼肌质量和力量。我们在32名有症状的患者中进行的首次随机假对照试验 PAD显示，有监督的腿部HT在临床上有意义地改善了感知的身体状况 功能正常。我们最近由R21赞助的初步研究表明，基于家庭的、无人监督的腿部HT是安全的 对有症状的PAD患者耐受性良好。根据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，以建立 持续12周的日常家庭腿部低血压对功能能力和生活质量的影响。患者被随机分配到 腿部热疗组(n=55)，每天用水循环裤进行90min的治疗 在假手术组(n=55)中，33℃的水将通过 裤子。主要的研究结果是基线和12分钟步行距离的变化。 一周的随访。次要结果包括腿部力量和疲劳性的变化，短期内的变化 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- 高血压影响肌肉力量和行走能力的水平机制。我们将评估骨骼 应用磁共振成像(MRI)和小腿活检的肌肉形态和血流量 肌肉。如果基于我们初步数据的结论得到证实，拟议的实验将 为新的、直接的方法的可行性和有效性提供一个基于证据的框架 改善PAD患者的功能表现和生活质量。鉴于其可访问性、可容忍性和易用性 用途：羟色胺具有快速翻译和临床应用的潜力，从而打开了新的 非侵入性PAD管理的地平线。 布鲁诺·罗吉尼，博士。

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.