Effects of forced exercise training on Parkinson's motor function

描述（由申请人提供）：本初步研究的目的是研究强迫运动对帕金森病（PD）患者帕金森运动体征的影响。目前的医学和外科治疗方法都很昂贵，而且有各种各样的副作用，可能会影响病人的生活质量。发展一种非药物、非手术的治疗方法来改善运动功能，将为目前的PD治疗方法提供一个有吸引力的辅助手段。动物研究表明，强迫运动可以改善运动功能，并具有神经保护作用。动物研究的令人鼓舞的结果尚未转化为PD患者。在动物和人类研究中使用的运动方式的差异，分别是强迫和自愿，可能是缺乏证据支持运动作为PD干预的原因。PD模型为PD患者使用强制运动干预提供了理论框架和理论依据。根据动物研究，运动激活减少可能限制PD患者以必要的速率产生自主运动的能力，以改善整体运动功能。我们开发了一种下肢强制运动模式来增强PD患者的自主运动，以帮助他们安全地实现大于其自主运动率的运动。我们的初步数据表明，完成8周强制运动干预的患者在临床运动评分评分方面提高了35%，而完成类似有氧强度的自愿运动干预的患者在临床评分方面没有改善。该项目的主要目的是评估和比较强迫运动和自愿运动对PD患者运动功能的影响。我们建议进行一项初步的前瞻性、单中心、单盲对照研究。这个初步的项目将是第一个使用临床和客观生物力学结果直接比较强迫和自愿运动对人类PD患者运动功能的影响。共有60例（每组20例）轻中度特发性PD患者将被随机分为自愿组、强迫组或不运动组。临床和生物力学评估将在五个时间点进行：基线、治疗中期、治疗结束（EOT）、EOT + 4和EOT + 8周。假设完成强制运动的患者与自愿和不运动组相比，运动功能会有全面的改善。如果强制运动显示有效，它可能成为药物或手术方法的可行替代或辅助治疗。拟议的循环干预很简单，可以自我指导，相对便宜（系统约2,500美元），可以立即转化为住院或门诊临床环境或患者家中。公共卫生相关性：这项研究的临床相关性是重要的，因为它解决了一种新颖和创新的运动干预治疗帕金森病的有效性。将收集初步数据，以评估使用强迫运动治疗帕金森病的疗效。拟议的强制运动干预增强了帕金森患者的自主运动，以帮助他们实现更大的运动率。动物研究表明，高强度的锻炼可以改善运动表现，并具有神经保护作用。将对完成8周强迫运动、自愿运动或不运动的患者进行运动功能的比较。据预测，与自愿或不运动相比，强迫运动对运动功能的改善更大。拟议的武力演习干预是安全且廉价的。在最小的空间和成本下，这种干预可以在大大小小的物理和职业治疗诊所以及患者家中进行复制。这种干预可能会导致帕金森病的更好治疗，并改善帕金森病患者的生活质量。社会将从这个项目中受益，因为患有其他神经系统疾病或中风的人也可能受到这些结果的积极影响。

DESCRIPTION (provided by applicant): The goal of this preliminary study is to examine the effect of forced-exercise on parkinsonian motor signs in patients with Parkinson's disease (PD). Current medical and surgical approaches are expensive and are associated with a variety of side effects that may compromise the patient's quality of life. The development of a non-drug, non- surgical therapeutic approach to improve motor function would provide an attractive adjunct to current PD treatment approaches. Animal studies have shown that forced- exercise improves motor function and has neuroprotective qualities. The promising results from animal studies have not been translated to patients with PD. Differences in exercise modality used in animal versus human studies, forced vs. voluntary respectively, may account for the lack of evidence supporting the use of exercise as an intervention for PD. Models of PD provide a theoretical framework and rationale for the use of a forced-exercise intervention for PD patients. Decreased motor activation may limit PD patients' ability to generate voluntary movements at rates necessary, based on animal studies, to improve global motor functioning. We developed a lower extremity forced-exercise paradigm to augment the voluntary movements of PD patients to assist them in safely achieving an exercise rate greater than their voluntary rate. Our Preliminary Data indicate that patients completing an 8-week forced-exercise intervention exhibit a 35 percent improvement in clinical motor rating scores whereas patients completing a voluntary exercise intervention, of similar aerobic intensity, exhibited no improvements in clinical ratings. The primary aim of this project is to assess and compare the effects of forced versus voluntary exercise on motor function in patients with PD. We propose to conduct a preliminary prospective, single-center, single-blind controlled study. This preliminary project will be the first to directly compare the effects of forced and voluntary exercise on motor function using clinical and objective biomechanical outcomes in human PD patients. A total of 60 (n=20 per group) mild to moderate idiopathic PD patients will be randomized to a voluntary, forced or no-exercise control group. Clinical and biomechanical assessments will be performed at five time points: Baseline, mid-treatment, end of treatment (EOT), EOT + 4 and EOT + 8 weeks. It is hypothesized that patients completing forced-exercise will exhibit a global improvement in motor function compared to the voluntary and no-exercise groups. If forced-exercise is shown effective, it could become a viable alternative or adjunct therapy to pharmacologic or surgical approaches. The proposed cycling intervention is simple, can be self-directed, is relatively inexpensive (~$2,500 for system) and could immediately be translated to a inpatient or outpatient clinical setting or a patient' home. PUBLIC HEALTH RELEVANCE: The clinical relevancy of this study is important as it addresses the effectiveness of a novel and innovative exercise intervention for the treatment of Parkinson's disease. Preliminary data will be gathered to assess the efficacy of using forced-exercise in the treatment of Parkinson's disease. The proposed forced-exercise intervention augments the voluntary movements of Parkinson's patients to assist them in achieving a greater rate of exercise. Animal studies suggest exercising at higher rates improves motor performance and has neuroprotective qualities. Comparisons in motor function will be made between patients completing eight weeks of forced, voluntary or no-exercise. It is predicted that forced-exercise will result in greater improvements in motor function than voluntary or no-exercise. The proposed force-exercise intervention is safe and inexpensive. With minimal space and costs the intervention could be replicated in large and small physical and occupational therapy clinics and in the home of the patient. This intervention will potentially lead to better treatment of Parkinson's disease and improve the quality of life of those suffering from Parkinson's. Society will benefit from this project as individuals suffering from other neurological disorders or stroke could also be positively impacted by these results.