Neuromuscular rehabilitation to improve function in older adults with PAD

神经肌肉康复可改善患有 PAD 的老年人的功能

• 批准号: 9387263
• 负责人: Steven J Prior
• 金额: $ 15.75万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2017-09-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387263
• 关键词: Acute; Address; Aerobic; Aerobic Exercise; Affect; Analysis of Covariance; Animals; Applications Grants; Area; Blood capillaries; Blood flow; Bone Marrow; Clinical; Clinical Management; Data; Development; Diffuse; Elderly; Gastrocnemius Muscle; Glucose; Goals; Growth Factor; Health Care Costs; Human; Impairment; Insulin; Intervention; Lead; Measures; Medical; Metabolic; Metabolism; Morbidity - disease rate; Muscle; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Operative Surgical Procedures; Outcome; Oxygen; Pain; Participant; Patients; Perfusion; Peripheral arterial disease; Physical Function; Physical Performance; Pilot Projects; Plasma; Quality of life; Race; Randomized; Rehabilitation therapy; Research; Research Design; Research Project Grants; Sampling; Skeletal Muscle; Spinal cord injury; Standardization; Stem cells; Stratification; Surface; Testing; Training; Translating; Translational Research; Treadmill Tests; Ultrasonography; Veterans; Walking; aging population; angiogenesis; artery occlusion; capillary; claudication; contrast enhanced; density; design; disability; exercise program; exercise rehabilitation; exercise training; frailty; functional improvement; functional loss; functional status; glucose metabolism; high risk; impaired glucose tolerance; improved; improved functioning; intervention effect; mortality; neuromuscular rehabilitation; neuromuscular stimulation; novel; older men; older patient; older women; patient oriented; performance tests; premature; primary outcome; programs; randomized trial; rehabilitation strategy; response; sex; skeletal; standard of care; trial design

Peripheral artery disease (PAD) and its associated declines in physical function and glucose metabolism affect nearly 20% of older adults and result in substantial health care costs. The current standard of care for PAD patients includes only medical management or surgical revascularization, but this does not sufficiently address functional and metabolic impairments related to impaired angiogenesis and capillary rarefaction. Aerobic exercise training (AEX) results in modest functional improvements in PAD patients, but does not restore functional status to that of healthy older adults. This may be attributable, in part, to a limited angiogenic response to AEX in PAD patients. Adjunct therapies such as neuromuscular electrical stimulation (NMES) may enhance skeletal muscle angiogenesis to improve function and metabolism in these patients. This study will test the hypothesis that AEX+NMES improves angiogenic growth factor expression, endothelial progenitor cell (EPC) mobilization, skeletal muscle capillary density, and muscle perfusion more than AEX or NMES alone, and that improvements in these mechanisms will translate to greater increases in ambulatory capacity and glucose metabolism in older PAD patients with impaired glucose tolerance (IGT). This will be tested through two aims. Aim 1: Determine the effects of AEX+NMES, AEX-only, and NMES-only compared to Control on skeletal muscle capillary density and associated angiogenic mechanisms. Aim 2: Determine whether the effects of the interventions on angiogenesis translate to improvements in muscle perfusion, ambulatory capacity, and glucose metabolism. We will study 48 older men and women with PAD and IGT (60- 75yrs, Fontaine Stage I-II PAD) randomized, with stratification by sex and race, to one of four groups (AEX+NMES, AEX-only, NMES-only, or Control; n=12/group). Before and after the 3-month interventions, participants will complete research testing consisting of: a) A standardized treadmill test to assess ambulatory capacity and calf muscle perfusion by contrast-enhanced ultrasound; b) Assessment of mobility function by modified physical performance test and 6-minute walk; c) Oral glucose tolerance test; d) Gastrocnemius muscle sampling to measure capillary density and angiogenic growth factor expression; and e) An acute bout of AEX or NMES to assess effects on circulating angiogenic growth factor levels and EPC mobilization. Repeated measures ANCOVA will be used to determine the effects of EX+NMES, NMES-only, and AEX-only compared to Control. This would be the first study to use NMES as an adjunct to AEX with the goal of improving muscle perfusion, physical function, and metabolism in older PAD patients with IGT. Moreover, this study design will assess the independent and combined effects of AEX and NMES on angiogenic mechanisms associated with any improvements in function and metabolism. This could lead to larger trials intended to improve the treatment of older PAD patients in order to reduce the loss of functional independence, rates of surgical intervention, morbidity and mortality.

周围动脉疾病（PAD）及其相关的身体机能下降和葡萄糖下降 代谢影响近20％的老年人，并带来了大量的医疗保健费用。当前标准 PAD患者的护理仅包括医疗管理或手术血运重建，但这不是 足够解决与血管生成受损和毛细血管受损有关的功能和代谢障碍 稀疏。有氧运动训练（AEX）导致PAD患者的功能改善，但 不会恢复健康老年人的功能状态。这可能部分归因于有限的 PAD患者对AEX的血管生成反应。辅助疗法，例如神经肌肉电刺激 （NME）可以增强骨骼肌血管生成，以改善这些患者的功能和代谢。 这项研究将测试AEX+NMES改善血管生长因子表达，内皮的假设 祖细胞（EPC）动员，骨骼肌毛细血管密度和肌肉灌注比AEX或 单独使用NME，这些机制的改善将转化为卧床的更大增加 葡萄糖耐受性受损（IGT）的老年PAD患者的容量和葡萄糖代谢。这将是 通过两个目标进行测试。 AIM 1：确定AEX+NME的影响，仅AEX-与NMES相比 控制骨骼肌毛细管密度和相关的血管生成机制。目标2：确定 干预措施对血管生成的影响是否转化为肌肉灌注的改善， 门诊能力和葡萄糖代谢。我们将研究48位具有PAD和IGT的年长男女（60-- 75yrs，Fontaine阶段I-II垫）随机分为性别和种族分层，为四组之一 （AEX+NME，仅AEX，仅NMES或对照； n = 12/组）。在三个月的干预措施之前和之后， 参与者将完成包括：a）标准化跑步机测试的研究测试 通过对比增强的超声检查能力和小腿肌肉灌注； b）通过 修改的身体绩效测试和6分钟步行路程； c）口服葡萄糖耐量测试； d）腹腔 肌肉采样以测量毛细血管密度和血管生长因子表达； e）急性回合 AEX或NME评估对循环血管生长因子水平和EPC动员的影响。 重复测量ANCOVA将用于确定EX+NME，仅NMES和仅AEX的影响 与对照相比。这将是第一次将NME作为AEX辅助的研究，目的是 改善IGT老年PAD患者的肌肉灌注，身体功能和代谢。而且，这 研究设计将评估AEX和NME对血管生成机制的独立和综合影响 与功能和代谢的任何改进相关。这可能会导致更大的试验 改善老年PAD患者的治疗，以降低功能独立性的丧失 手术干预，发病率和死亡率。