Forced Exercise: A New Therapy for the Treatment of Parkinson's Disease

描述（由申请人提供）：Alberts及其团队（克利夫兰诊所）进行的一项小型试点研究表明，在改善帕金森病（PD）患者的运动功能方面，持续强迫运动（FE）可能与药物治疗或手术植入微电极进行脑深部刺激一样有效或更有效。在FE中，一个人以超过他身体能够达到和保持的速度积极锻炼。在Alberts的研究中，患者每周完成3次40分钟FE训练，持续8周，使用固定双人自行车，“教练”提供约75%的能量，以维持80-90 rpm的节奏，患者提供足够的能量，以维持其年龄最大心率的80%。令人惊讶的是，这种方案改善了上半身和下半身的运动功能。不幸的是，这种FE方案的商业化将是非常昂贵的，需要一个健康的教练员来操纵固定的串列的前座，并且需要一个监督员来确保达到并保持FE的目标水平。RSS工业公司建议设计，建造和台架测试的性能的机动运动周期原型，治疗PD，能够取代的物理输入提供的教练在阿尔伯茨的FE方案。起点将是现有的Theracomp，这是一种由RSS开发和制造的固定的、软件控制的电机驱动的治疗性锻炼系统，于2002年推出，供有严重身体残疾的个人使用。在为期1年的SBIR第一阶段工作计划期间实施的创新和增强将使原型Theraceton PD能够：1）允许骑手通过过驱动电机实现FE; 2）使用骑手的心率作为控制回路的一部分，以在需要更多踩踏努力以维持目标心率（和FE）以及电机可以提供努力时发出信号。具体目标包括：用可反向驱动的低阻力齿轮系统替换标准Theracetum上现有的齿轮箱。SA 2：开发和集成心率监测器、电子元件、增强的GUI和必要的软件. SA 3：构建并发布测试3个额外的原型Theracetone PD装置，用于SBIR II期FE方案的临床疗效测试（共4个装置; 2个临床研究中心各1个主要和1个备用）。可行性/进展标准：Theraceton PD原型在FE期间实现的心率和踏板节奏值必须在Alberts初步研究中报告的值范围的10%以内。将不会尝试确定FE方案的有效性，因为这将在SBIR II期中解决。 公共卫生相关性：帕金森病（PD）患者的上半身和下半身运动功能逐渐丧失，药物治疗随着时间的推移变得越来越无效。最近的一项试点研究表明，在双人自行车上进行强制锻炼（其中第二名骑手以远高于PD患者自愿努力所能达到的速度辅助踏板）可以使运动功能的全身改善至少与晚期疾病患者的药物治疗一样好，甚至可能更好。本文提出的工作旨在创建Theraceton PD，这是一种使用电机代替第二个骑手提供的体力的固定锻炼周期，其长期目标是使强迫锻炼成为更广泛的PD患者群体可负担得起的（<5000美元）选择。

DESCRIPTION (provided by applicant): A small pilot study by Alberts and team (Cleveland Clinic) suggests that sustained forced exercise (FE) may be as or more effective than medication or surgical implantation of microelectrodes for deep brain stimulation in improving motor function in individuals with Parkinson's disease (PD). In FE, an individual actively exercises at a rate in excess of that which (s)he is physically able to attain and maintain by (her)himself. In the Alberts' study, patients completed three 40 min FE sessions/week for 8 weeks, using a stationary tandem bicycle on which a "trainer" provided ~75% of the energy required to maintain a cadence of 80-90 rpm and the patient provided sufficient energy to maintain a target heart rate 80% of maximum for their age. Somewhat surprisingly, this regimen improved upper as well as lower body motor function. Unfortunately, commercialization of this FE regimen would be prohibitively expensive, requiring a healthy trainer to man the front seat of the stationary tandem and a supervisor to insure the targeted level of FE was reached and maintained. RSS Industries, Inc. proposes to design, build and bench test the performance of a motorized exercise cycle prototype, the Theracycle PD, able to replace the physical input provided by the trainer in the Alberts' FE regimen. The starting point will be the existing Theracycle, a stationary, software-controlled motor driven therapeutic exercise system developed and manufactured by RSS and launched in 2002 for use by individuals with significant physical disabilities. Innovations and enhancements to be implemented during the 1 year SBIR Phase I work plan will enable the prototype Theracycle PD to: 1) allow the rider to achieve FE by overdriving the motor; and 2) use the rider's heart rate as part of a control loop to signal when more pedaling effort is required to maintain target heart rate (and FE) and when the motor can provide the effort. Specific aims (SAs) include: SA1. Replace existing gear box on a standard Theracycle with a back-drivable, low resistance gearing system. SA 2: Develop and integrate a heart rate monitor, electronic components, enhanced GUI and requisite soft- ware. SA 3: Build and release test 3 additional prototype Theracycle PD units for use in clinical efficacy testing of FE regimens in SBIR Phase II (4 units total; 1 primary and 1 backup for each of 2 clinical sites). Feasibility/Progression Criteria: The heart rate and pedal cadence values achieved during the FE period on the Theracycle PD prototypes must be within 10% of the range of values reported in the Alberts' pilot study. No attempt will be made to ascertain effectiveness of the FE regimen as that will be addressed in SBIR Phase II. PUBLIC HEALTH RELEVANCE: Individuals with Parkinson's disease (PD) suffer progressive loss of upper and lower body motor functions, for which drug therapy becomes less and less effective over time. A recent pilot study suggests that forced exercise on a tandem bicycle (in which a second rider aids in pedaling at a rate well above that achievable by a PD patient's voluntary effort) can produce whole body improvements in motor function at least as good as and possibly better than those achieved by medication in patients with advanced disease. The work proposed here is designed to create the Theracycle PD, a stationary exercise cycle using a motor to replace the physical effort provided by the second rider, with the long term goal of making forced exercise an affordable (<$5000) option available to a much wider group of PD patients.