CLINICAL TRIAL: THE UTILITY OF UPPER EXTREMITY AEROBIC TRAINING FOR CRITICAL LIM

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 这项研究挑战了运动训练在严重外周动脉疾病患者中不可行或有益的范式。本研究的主要目的是确定12周、每周3次监督手臂测力计训练对重度跛行或缺血性静息痛（严重肢体缺血，CLI）患者下肢组织氧合、上肢运动能力、步行距离以及内皮功能障碍和炎症标志物的可行性和耐受性。CLI是外周动脉疾病（PAD）的最严重形式，其由在腿部动脉中积聚斑块的进行性动脉粥样硬化疾病引起。 当腿部组织的血液供应不足时，即使在休息时也会发生CLI，从而导致疼痛。 这种功能不全导致缺血性静息痛，最终导致缺血性溃疡、坏疽，甚至截肢。 CLI每年影响约500- 1，000/百万人，并使用大量的卫生保健资源。 CLI与衰老有关;在420万患有CLI的美国人中，有250万人年龄超过70岁。严重外周动脉疾病患者的总体预后非常差。在诊断为严重肢体缺血一年后，大约25%的患者将截肢，另外25%的患者将死亡。5年内截肢率为40%，死亡率为40-70%。大约25%的CLI患者足够稳定，因此不需要立即干预或不适合血运重建。 这些是替代治疗的潜在候选者。 有证据表明，上肢运动可以改善步行距离，并提供与下肢运动相似的额外治疗益处。然而，没有已知的研究已经测试了上半身锻炼对CLI患者的影响。 对上身运动的全身反应可能对下肢产生有益影响，从而减少或缓解静息痛以及改善全身炎症和内皮功能障碍的标志物。 这可能会减少对侵入性手术的需求，并减少对医疗资源的利用。 受试者接受筛选访视，获得知情同意书，审查病史，并完成几份生活质量问卷。 在整个研究期间监测心率、节律和血压。 在运动之前和之后收集血液样本，以及足部组织的氧合。 测量腿部血液循环的踝关节血压测试是根据既定的指南进行的。 然后，参与者使用手动自行车进行上肢有氧运动评估。 在整个测试过程中收集呼吸气体测量值，以确定心肺健康和调节。 医生监督测试的各个方面。 参与者被分配到练习组或对照组。 锻炼组每周锻炼三次，持续12周，使用手动自行车，强度由初始测试确定。 这些训练包括5分钟的热身，然后是60分钟的间歇性运动，然后是5分钟的冷静，总共70分钟。 在整个锻炼过程中监测心率、节律和血压。 对照组参与者遵循医生的建议并继续常规护理;这些参与者每月联系一次，以提供鼓励并回答可能出现的任何问题。 在12周结束时，所有参与者都经历了与初始筛选访视期间相同的测试程序。这项研究将为这种功能衰弱的高危人群提供一种具有成本效益的治疗选择，并允许评估干预的可行性和耐受性以及疗效，所有这些都将指导后续的更大规模的试验。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study challenges the paradigm that exercise training is not feasible or beneficial in patients with severe peripheral arterial disease. The primary aims of this study are to determine the feasibility and tolerability of 12 weeks, 3 times per week of supervised arm ergometry training on tissue oxygenation of the lower extremities, upper extremity exercise capacity, walking distance, and markers of endothelial dysfunction and inflammation in patients with severe claudication or ischemic rest pain (Critical limb ischemia, CLI). CLI is the most severe form of peripheral arterial disease (PAD), which is caused by progressive atherosclerotic disease that builds up plaque in the arteries of the legs. CLI occurs when there is insufficient blood supply to the tissue of the legs causing pain, even at rest. This insufficiency leads to ischemic rest pain and eventually to ischemic ulcers, gangrene, and even amputation. CLI affects approximately 500-1,000/million individuals per year and uses a significant amount of health care resources. CLI is associated with aging; of the 4.2 million Americans with CLI, 2.5 million are over the age of 70. The overall prognosis for patients with severe peripheral arterial disease is very poor. One year after a diagnosis with critical limb ischemia, approximately 25% of patients will have had an amputation and another 25% will have died. There is a 40% amputation rate and a 40-70% mortality rate over 5 years. Approximately 25 % of individuals with CLI are sufficiently stable so that immediate intervention is not required or they are not suitable for revascularization. These are the potential candidates for alternative therapeutic treatment. There is evidence that upper body exercise improves walking distance and provides additional therapeutic benefits similar to lower extremity exercise. However, there are no known studies that have tested the effect of upper body exercise in individuals with CLI. The systemic response to upper body exercise could have beneficial effects on the lower extremities, resulting in reduction or alleviation of rest pain as well as improvement in markers of systemic inflammation and endothelial dysfunction. This may reduce the need for invasive procedures and decrease the utilization on health care resources. The participants undergo a screening visit where informed consent is obtained, medical history is reviewed, and several quality of life questionnaires are completed. Heart rate, rhythm, and blood pressure are monitored throughout the study. Blood samples are collected before and after exercise, as well as tissue oxygenation in the feet. An ankle blood pressure test that measures circulation to the legs is performed according to established guidelines. The participant then undergoes an assessment of upper extremity aerobic exercise to exhaustion using a hand bike. Respiratory gas measures are collected throughout the test to determine cardiopulmonary fitness and conditioning. A physician supervises all aspects of the testing. The participants are assigned to the exercise or the control group. The exercise group exercises three times per week for 12 weeks using the hand bike at an intensity determined by the initial test. The sessions consist of five minutes of warm up followed by intermittent exercise for 60 minutes followed by five minutes of cool down for a total of 70 minutes. Heart rate and rhythm and blood pressure are monitored throughout the exercise sessions. The control group participants follow their physician¿s recommendations and continue usual care; these participants are contacted once per month to provide encouragement and to answer any questions that may arise. At the completion of 12 weeks all participants undergo the same testing procedures as during the initial screening visit. This study will provide insight into a cost effective therapeutic option for this functionally debilitated high-risk population, and permit assessment of the feasibility and tolerability, and efficacy of the intervention, all of which will direct subsequent, larger trials.