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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究挑战了这样的范式，即运动训练对患有严重外周动脉疾病的患者是不可行的或有益的。这项研究的主要目的是确定每周3次、12周的有监督的手臂测功仪训练对严重跛行或缺血性静息痛(严重肢体缺血，CLI)患者的下肢组织氧合、上肢运动能力、步行距离以及内皮功能障碍和炎症指标的可行性和耐受性。CLI是最严重的外周动脉疾病(PAD)，由进行性动脉粥样硬化性疾病引起，在腿部动脉形成斑块。当腿部组织供血不足时会发生CLI，导致疼痛，即使在休息时也是如此。这种功能不全会导致缺血性休息疼痛，最终导致缺血性溃疡、坏疽，甚至截肢。CLI每年影响大约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250万人超过70岁。严重外周动脉疾病患者的总体预后非常差。在被诊断为严重肢体缺血一年后，大约25%的患者将接受截肢手术，另有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。这些都是替代治疗的潜在候选者。有证据表明，上半身运动可以改善步行距离，并提供类似于下肢运动的额外治疗益处。然而，目前还没有已知的研究测试上半身锻炼对CLI患者的影响。对上半身运动的全身反应可能会对下肢产生有益的影响，从而减少或缓解休息疼痛，并改善全身炎症和内皮功能障碍的标志。这可能会减少对侵入性程序的需求，并减少对卫生保健资源的利用。 参与者接受筛查访问，在那里获得知情同意，回顾病史，并填写几份生活质量问卷。在整个研究过程中都会监测心率、节律和血压。在运动前和运动后采集血液样本，以及足部组织氧合。测量腿部血液循环的脚踝血压测试是根据既定的指南进行的。然后，参与者使用手骑自行车进行上肢有氧运动的评估，直到筋疲力尽。在整个测试过程中收集呼吸气体测量，以确定心肺健康和调节。医生监督检查的各个方面。 参与者被分配到锻炼组或对照组。运动组每周锻炼三次，持续12周，强度由最初的测试确定。训练包括5分钟热身，然后是间歇性运动60分钟，然后是5分钟降温，总共70分钟。在整个锻炼过程中，都会监测心率、节奏和血压。对照组参与者遵循S医生的建议，继续进行常规护理；每月联系这些参与者一次，以提供鼓励并回答可能出现的任何问题。在12周结束时，所有参与者都要接受与最初筛查访问时相同的测试程序。这项研究将为这一功能衰弱的高危人群提供具有成本效益的治疗选择，并允许评估干预的可行性、耐受性和有效性，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.