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

描述(申请人提供)：艾伯茨和团队(克利夫兰诊所)进行的一项小型试点研究表明，在改善帕金森氏病(PD)患者的运动功能方面，持续强迫运动(FE)可能与药物或外科手术植入脑深部微电极一样有效或更有效。在体能训练中，一个人的积极运动速度超过了S自己身体所能达到和维持的水平。在Alberts的研究中，患者每周完成三次40分钟的FE训练，持续8周，使用固定的串联自行车，在这种自行车上，“训练员”提供大约75%的能量来维持80-90rpm的节奏，患者提供足够的能量来维持他们年龄最大心率的80%。有些令人惊讶的是，这种方法改善了上半身和下半身的运动功能。不幸的是，这种FE方案的商业化成本将高得令人望而却步，需要一名健康的教练员来操作固定串联的前排座位，并需要一名监督员来确保达到并维持目标水平的FE。RSS Industries，Inc.提议设计、制造并在台上测试一款摩托车运动自行车原型Theraccle PD的性能，该原型能够在艾伯茨的FE方案中取代训练者提供的身体输入。起点将是现有的Theraccle，这是一种由RSS开发和制造的静止的、由软件控制的马达驱动的治疗运动系统，于2002年推出，供严重肢体残疾的个人使用。在为期一年的SBIR第一阶段工作计划期间将实施的创新和增强将使Theraccle PD原型能够：1)允许骑手通过超速驱动电机来实现FE；2)使用骑手的心率作为控制循环的一部分，以指示何时需要更多的踏板努力来保持目标心率(和FE)，以及何时电机可以提供努力。具体目标(SA)包括：SA1。将标准Theraccle上的现有变速箱更换为可向后驱动的低阻力齿轮传动系统。SA 2：开发和集成心率监测器、电子元件、增强的图形用户界面和必要的软件。SA 3：构建和发布测试用于SBIR第二阶段FE方案临床疗效测试的另外3个原型Theraccle PD单元(共4个单元；2个临床站点各1个主要单元和1个备份单元)。可行性/进展标准：Theraccle PD样机在FE期间实现的心率和踏板节奏值必须在Alberts试验性研究报告的10%范围内。不会尝试确定FE方案的有效性，因为这将在SBIR第二阶段解决。 公共卫生相关性：帕金森氏病(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不有效。最近的一项初步研究表明，在双人自行车上进行强迫运动(即第二个骑手帮助骑自行车的速度远远高于PD患者自愿完成的速度)可以产生全身运动功能的改善，至少与晚期疾病患者的药物治疗一样好，甚至可能更好。这里提出的工作是为了创造Theraccle PD，这是一种固定的运动自行车，使用马达来取代第二个骑手提供的体力，长期目标是让强迫运动成为更广泛的PD患者群体可以负担得起的选择(5000美元)。

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.