The effects of a novel, non-ischemic and pain-free exercise intervention in peripheral artery disease

项目摘要/摘要 目标。我们的目标是在我们的初步工作的基础上，建立一个非缺血锻炼(NICE)计划 将更好的治疗外周动脉疾病(PAD)患者，以改善步行能力，与健康有关 生活质量、微血管功能和全身血管生物标记物高于标准疼痛 锻炼计划。 明确的目标。我们建议检验我们的中心假设，即NICE干预在没有 诱发腿部缺血及其破坏性后遗症将是增加高峰步行的一种优越的运动范式 通过在以下方面的更大改进，时间和HRQOL超过标准的缺血和痛苦运动范例 微血管机制。这一与临床相关的假设将通过以下目标进行检验： 目的1(运动结果)比较PAD患者步行和HRQL的变化 随机分为两组，一组是慢走计划，另一组是标准的缺血痛苦运动计划。 目的2a(血管结局)比较两组患者局部微血管功能的变化。 遵循NICE方案和标准的患者的肢体、炎症和氧化应激 缺血和痛苦的程序。 目的2b(探索性目的)探讨局部微血管功能和全身功能的变化 血管生物标志物与NICE和标准步行高峰时间变化相关 计划，以及在NICE计划之后，这种联系是否会更强。 方法：研究方法。这是一项为期3个月的、以患者为导向的、翻译的、随机比较的有效性研究 对照试验。100名患者将被随机分为NICE方案(N=50)或标准方案 锻炼方案(N=50)。所有患者将在有监督的情况下进行3个月的平板步行。患者随机化 TO NICE程序将以每小时约1.4英里的低速间歇行走，仅需2-3分钟 不会引起跛行疼痛。随机接受标准方案的患者将以间歇性的速度行走 速度约为每小时2英里，几乎是最大的跛行疼痛。 临床意义。如果成功，这个由慢节奏步行组成的好计划 不引起腿部缺血或疼痛将是一种新颖和创新的锻炼计划，并将成为锻炼的范例 最佳选择，以改善高峰步行时间、HRQL、局部微血管功能、炎症和氧化 PAD患者的应激反应。这些改进可能会影响PAD的临床进程，使其更健康和 更积极的生活方式。

PROJECT SUMMARY/ABSTRACT Objective. Our objective is to build on our preliminary work that a Non-IsChemic Exercise (NICE) program will be a better treatment for patients with peripheral artery disease (PAD) to improve ambulation, health-related quality of life (HRQoL), microvascular function, and systemic vascular biomarkers than a Standard painful exercise program. Specific Aims. We propose to test our central hypothesis that the NICE intervention performed without inducing leg ischemia and its’ damaging sequela will be a superior exercise paradigm to increase peak walking time and HRQoL more than the Standard ischemic and painful exercise paradigm via greater improvement in microvascular mechanisms. This clinically relevant hypothesis will be tested through the following aims: Aim 1 (Exercise Outcomes) To compare the changes in ambulation and HRQoL in PAD patients randomized to either the NICE slow walking program or to the Standard program of ischemic and painful exercise. Aim 2a (Vascular Outcomes) To compare the changes in local microvascular function of the lower extremities, inflammation and oxidative stress in patients following the NICE program, and following the Standard ischemic and painful program. Aim 2b (Exploratory Aim) To explore whether the changes in local microvascular function and systemic vascular biomarkers are associated with the changes in peak walking time following the NICE and Standard programs, and whether the association is stronger following the NICE program. Methods. This is a 3-month, patient-oriented, translational, comparative effectiveness randomized controlled trial. One-hundred patients will be randomized into either the NICE program (N=50) or the Standard exercise program (N=50). All patients will perform supervised treadmill walking for 3 months. Patients randomized to the NICE program will walk intermittently at a slow speed of approximately 1.4 mph for only 2-3 minute bouts that do not elicit claudication pain. Patients randomized to the Standard program will walk intermittently at a speed of approximately two mph to near maximal claudication pain. Clinical Significance. If successful, the NICE program which consists of slow-paced walking that does not elicit leg ischemia or pain will be a novel and innovative exercise program, and will be the exercise paradigm of choice to optimally improve peak walking time, HRQoL, local microvascular function, inflammation, and oxidative stress in PAD patients. These improvements could impact the clinical course of PAD by leading to healthier and more active lifestyles.