Post-revascularization rehabilitation to improve function in Veterans with PAD

 描述（由申请人提供）： 外周动脉疾病（PAD）及其相关的身体功能下降损害了近20%的老年退伍军人的生活质量（QOL），并导致大量的VA医疗保健费用。血运重建解决了解剖病理学问题，但不能恢复活动功能和QOL。最佳治疗可能需要血运重建后康复，以解决骨骼肌中的残留缺陷，例如毛细血管密度降低，这限制了功能;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QOL，神经肌肉电刺激（NMES）增加肌肉中的血流量和血管生成，这可能通过增加肌肉灌注来增强功能。总之，这两种疗法可能以互补的方式起作用，以改善血管重建后PAD老年退伍军人的结局。本研究检验了以下假设：监督运动训练和NMES（运动+NMES）的组合将比标准治疗更能改善运动功能、行走能力和QOL，这些改善是通过血管生成、毛细血管密度和血管重建后PAD退伍军人肌肉灌注增加等机制实现的。这将通过两个目标来检验。目标1：确定运动训练和NMES对接受PAD血管内血运重建术的中老年患者的活动功能和QOL的影响。将使用改良体能测试（MPPT）、6分钟步行测试和标准化跑步机测试评估移动功能和步行能力。将使用一般（SF-36）和疾病特异性（VascuQoL）问卷评估QOL。目标二：通过测量小腿肌肉灌注（超声造影）和血氧饱和度（StO 2，近红外光谱法）以及腓肠肌毛细血管密度和血管生成生长因子（VEGF和bFGF）表达，确定运动和NMES干预对骨骼肌肌肉灌注和潜在血管生成机制的影响。 我们将招募计划接受经皮血运重建术的PAD（方丹IIb-III期）退伍军人（50-80岁）。受试者将完成研究测试，包括：a）评估移动功能（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（跛行发作时间和峰值步行时间）、小腿肌肉灌注和StO 2; c）腓肠肌穿刺活检，以测量毛细血管密度和血管生成生长因子表达。受试者将在血运重建前接受基线测试（肌肉活检除外），并将在血运重建后2-3周重复研究测试，以确定仅血运重建对功能结局的影响。血运重建后检测后，52例患者将在年龄（± 5岁）和性别匹配的2x2研究设计中随机分配至4组之一（仅接受运动治疗、仅接受NMES治疗、运动+NMES治疗或标准治疗; n=13/组）。在完成3个月的干预后，参与者将重复所有测试，以确定干预措施与标准护理相比的效果。 这项以患者为导向的研究使用了标准化康复计划在血管内血运重建后PAD退伍军人中的新应用，以及NMES治疗作为这些患者运动康复的替代或辅助的新应用。这项研究有可能提供第一个证据，证明运动+NMES联合治疗通过肌肉机制（包括血管生成和肌肉灌注增加）改善血管重建后PAD患者的身体功能和QOL。这可能会导致更大规模的试验，旨在改变PAD的管理，以最终降低老年退伍军人的再干预率，发病率和死亡率。这种干预措施可以很容易地在医疗中心传播，并可能减少与PAD后果相关的残疾和医疗保健费用。

 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.