Post-revascularization rehabilitation to improve function in Veterans with PAD

血运重建后康复可改善患有 PAD 的退伍军人的功能

• 批准号: 9031931
• 负责人: Steven J Prior
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9031931
• 关键词: Address; Adjuvant; Adult; Aerobic; Aerobic Exercise; Affect; Age; Age-Years; Award; Biopsy; Blood Vessels; Blood capillaries; Blood flow; Cardiovascular system; Clinical; Comorbidity; Data; Defect; Disease; Effectiveness; Elderly; Electric Stimulation Therapy; Enrollment; Exercise; FGF2 gene; Gastrocnemius Muscle; Goals; Growth; Health; Health Care Costs; Healthcare; Intervention; Lead; Limb structure; Measures; Medical center; Metabolic; Modality; Morbidity - disease rate; Muscle; Muscle Contraction; Near-Infrared Spectroscopy; Needle biopsy procedure; Outcome; Oxygen; Pain in lower limb; Participant; Pathology; Patients; Perfusion; Peripheral arterial disease; Physical Function; Physical Performance; Population; Procedures; Quality of life; Questionnaires; Randomized; Rehabilitation therapy; Research; Research Design; Research Project Grants; Risk Factors; SF-36; Skeletal Muscle; Staging; Testing; Therapeutic; Time; Training; Translational Research; Treadmill Tests; Ultrasonography; Vascular Endothelial Growth Factors; Veterans; Walking; Work; angiogenesis; capillary; claudication; contrast enhanced; density; design; disability; exercise intervention; exercise program; exercise rehabilitation; exercise training; experience; functional outcomes; improved; improved functioning; improved mobility; improved outcome; intervention effect; middle age; mortality; neuromuscular stimulation; novel; older patient; patient oriented; patient oriented research; performance tests; premature; primary outcome; programs; public health relevance; randomized trial; rehabilitation strategy; secondary outcome; sex; skeletal; standard care; standard of care; treatment strategy

 DESCRIPTION (provided by applicant): Peripheral artery disease (PAD) and its associated declines in physical function impair quality of life (QOL) in nearly 20% of older veterans and result in substantial VA health care costs. Revascularization addresses the anatomical pathology, but does not restore mobility function and QOL. Optimal therapy may require post- revascularization rehabilitation to address lingering defects in skeletal muscle, such as reduced capillary density, that limit function; however, the current standard of care after revascularization does not include rehabilitation. Exercise training improves ambulatory capacity and QOL in early stage PAD, and neuromuscular electrical stimulation (NMES) increases blood flow and angiogenesis in muscle which may enhance function by increasing muscle perfusion. Together, these two therapies may work in a complementary manner to improve outcomes in older veterans with PAD after revascularization. This study tests the hypothesis that the combination of supervised exercise training and NMES (Exercise+NMES) will improve mobility function, ambulatory capacity, and QOL more than standard care, and these improvements occur through mechanisms including increases in angiogenesis, capillary density, and muscle perfusion in veterans with PAD after revascularization. This will be tested through two aims. Aim 1: Determine the effects of exercise training and NMES on mobility function and QOL in middle-aged to older patients who have undergone endovascular revascularization for PAD. Mobility function and ambulatory capacity will be assessed using the modified physical performance test (MPPT), 6-minute walk test, and a standardized treadmill test. QOL will be assessed using general (SF-36) and disease-specific (VascuQoL) questionnaires. Aim 2: Determine the effects of the exercise and NMES interventions on muscle perfusion and underlying angiogenic mechanisms in skeletal muscle by measuring calf muscle perfusion (contrast-enhanced ultrasound) and oxygen saturation (StO2, by near-infrared spectroscopy), as well as gastrocnemius muscle capillary density and expression of angiogenic growth factors (VEGF and bFGF). We will enroll veterans (50-80 years of age) with PAD (Fontaine Stage IIb-III) who are planned for percutaneous revascularization. Participants will complete research testing consisting of: a) Assessment of mobility function (MPPT and 6-minute walk) and QOL (SF-36 and VascuQoL questionnaires); b) Treadmill tests to assess ambulatory capacity (claudication onset time and peak walking time), calf muscle perfusion and StO2; and c) A gastrocnemius needle biopsy to measure capillary density and angiogenic growth factor expression. Participants will undergo baseline testing prior to revascularization (with the exception of the muscle biopsy) and will repeat research testing 2-3 weeks after revascularization to determine the effect of only revascularization on functional outcomes. After post-revascularization testing, 52 patients will be randomized to one of four groups (Exercise-only, NMES-only, Exercise+NMES, or Standard Care; n=13/group) in a 2x2 study design with matching for age (± 5 yrs) and sex. After completion of the 3-month intervention, participants will repeat all tests to determine the effects of the interventions compared to standard care. This patient-oriented research uses the novel application of standardized rehabilitation programs to veterans with PAD after endovascular revascularization, and the novel application of NMES therapy as an alternative or adjuvant to exercise rehabilitation in these patients. This study has the potential to provide the first evidence that combined Exercise+NMES improves, physical function and QOL in PAD patients after revascularization through muscle mechanisms including increases in angiogenesis and muscle perfusion. This could lead to larger trials intended to alter the management of PAD in order to ultimately reduce the rates of re- intervention, morbidity and mortality in older veterans. Such interventions could be easily disseminated across medical centers and potentially reduce disability and health care costs related to the consequences of PAD.

 描述（由申请人提供）： 周围动脉疾病 (PAD) 及其相关的身体功能下降会损害近 20% 的老年退伍军人的生活质量 (QOL)，并导致大量的退伍军人事务部医疗费用。血运重建可以解决解剖病理学问题，但不能恢复活动功能和生活质量。最佳治疗可能需要血运重建后康复，以解决骨骼肌中长期存在的缺陷，例如限制功能的毛细血管密度降低；然而，血运重建后的当前护理标准不包括康复。运动训练 改善早期 PAD 的行走能力和生活质量，神经肌肉电刺激 (NMES) 可以增加肌肉中的血流量和血管生成，从而可以通过增加肌肉灌注来增强功能，这两种疗法可以以互补的方式发挥作用，以改善老年退伍军人的治疗结果。这项研究检验了以下假设：监督运动训练和 NMES（运动+NMES）相结合将比标准护理更改善运动功能、行走能力和生活质量，并且这些改善正在发生。通过血运重建后 PAD 退伍军人的血管生成、毛细血管密度和肌肉灌注增加等机制，这将通过两个目标进行测试：确定运动训练和 NMES 对中老年人活动功能和生活质量的影响。因 PAD 接受血管内血运重建的患者将使用改良体能测试 (MPPT)、6 分钟步行测试和标准化跑步机生活质量测试来评估患者的活动功能和行走能力。将使用一般 (SF-36) 和疾病特异性 (VascuQoL) 问卷进行评估 目标 2：通过测量小腿肌肉灌注（对比增强）确定运动和 NMES 干预对骨骼肌灌注和潜在血管生成机制的影响。超声）和氧饱和度（StO2，通过近红外光谱），以及腓肠肌毛细血管密度和血管生成的表达我们将招募计划进行经皮血运重建的 PAD（Fontaine IIb-III 期）退伍军人（50-80 岁），他们将完成包括以下内容的研究测试： a) 活动功能评估 参与者（ MPPT 和 6 分钟步行）和 QOL（SF-36 和 VascuQoL 问卷）； b) 跑步机测试，以评估行走能力（跛行开始时间和峰值步行时间）、小腿肌肉灌注和 StO2；和 c) 腓肠肌针活检，以测量毛细血管密度和血管生成生长因子表达。参与者将在血运重建前接受基线测试（肌肉活检除外），并在血运重建后 2-3 周重复研究测试。确定仅血运重建对功能结果的影响在血运重建后测试后，52 名患者将被随机分为四组之一（仅运动、仅 NMES、运动+NMES、或标准护理；n=13/组），采用年龄（± 5 岁）和性别匹配的 2x2 研究设计。 完成 3 个月的干预后，参与者将重复所有测试，以确定干预措施与对照组的效果。这项以患者为导向的研究将标准化康复计划应用于血管内血运重建后的 PAD 退伍军人，并将 NMES 疗法作为这些患者运动康复的替代疗法或辅助疗法。第一个有证据表明，运动+NMES 联合治疗通过肌肉机制（包括增加血管生成和肌肉灌注）进行血运重建后，可以改善 PAD 患者的身体功能和生活质量，这可能会导致更大规模的试验，旨在改变 PAD 的治疗，以最终降低再血管化率。 - 老年退伍军人的干预、发病率和死亡率。此类干预措施可以很容易地在医疗中心传播，并有可能减少与 PAD 后果相关的残疾和医疗费用。