Exploratory study of different doses of endurance exercise in people with Parkins

描述(申请人提供)：在过去的十年里，一个新兴的文献表明，运动对帕金森氏病(PD)患者和PD动物模型都有治疗益处，特别是当动物进行高强度运动时。尽管已经进行了许多研究，传统观点承认运动的好处，但还没有研究表明：1)运动对尚未开始多巴胺替代疗法的帕金森病患者(新手帕金森病患者)的好处，以及2)“适度”运动与“剧烈”运动对减缓新手帕金森病患者帕金森病症状进展的剂量-反应效应。因此，长期目标是确定运动是否应该作为新手帕金森病的一线治疗。作为实现我们长期目标的第一步，我们将在六个月内对两种强度的耐力锻炼进行多中心、随机、对照、单盲研究；我们还将有一个对照的“不锻炼”组。两种运动水平分别是中等强度(60%-65%最大心率下的4天/周)和剧烈运动(80%-85%最大心率下的4天/周)。我们提出了三个目标。第一个目标是找出患者是否可以进行更高强度的运动。目标2是找出这两种运动强度中的一种或两种是否产生了与统一帕金森氏病评定量表(UPDRS)中有意义的临床变化一致的益处(非徒劳)。目标3是记录与临床试验相关的关键反应，如不良事件和自然减员。在这项研究完成后，如果无效性试验成功，我们将处于进行III期临床试验的有利地位。E根据这项探索性研究的结果，目前设想了6种可能的成功情景。这些情景清楚地表明了在第三阶段临床试验中将测试哪些参数。TH方案不仅基于无效性试验的结果(目标2)，而且还基于达到的最大心率百分比和平均锻炼天数(目标1)。所有这三个组成部分对于计划下一项研究帕金森病的锻炼都是至关重要的。我们也认识到试验可能会被宣布为徒劳，这将迫使我们重新考虑运动对帕金森病的治疗价值

DESCRIPTION (provided by applicant): Over the past decade a burgeoning literature suggests that exercise has a therapeutic benefit in both patients with Parkinson's disease (PD) and in animal models of PD, especially when animals exercise at high intensity. Although many studies have been conducted and conventional wisdom acknowledges the beneficial effects of exercise, there have been no studies of: 1) the benefits of exercise in PD patients who have not yet started dopamine replacement therapy (patients with de novo PD), and 2) the dose-response effects of "moderate" versus "vigorous" exercise to attenuate the progression of PD symptoms in patients with de novo PD. Accordingly, the long-range goal is to determine whether exercise should be first-line therapy for de novo PD. As the first step in accomplishing our long-term goal, we will conduct a multi-center, randomized, controlled, single-blinded study of two intensities of endurance exercise over six months; we will also have a control "no- exercise" group. The two levels of exercise are moderate (4 days/wk at 60%-65% HRmax) and vigorous (4 days/wk at 80%-85% HRmax). We are proposing three aims. Aim 1 is to find out if patients can exercise at the higher level of intensity. Aim 2 is to find out if either or both of the exercie intensities yield benefits consistent with meaningful clinical change in the Unified Parkinson's Disease Rating Scale (UPDRS) (non-futility). Aim 3 is to document key responses associated with clinical trials, such as adverse events and attrition. Upon the completion of this study we will be well-positioned to conduct a phase III clinical trial if the futility trial is successful. e currently envision 6 possible successful scenarios based on the results of this exploratory study. These scenarios clearly indicate what parameters will be tested in the phase III clinical trial. Th scenarios are based not only on the outcome of the futility trial (Aim 2) but also on %HRmax attained and average number of days exercised (Aim 1). All 3 components are critical in planning the next study investigating exercise in PD. We also recognize the possibility the trial will be declared futile, which will force us to reconsider the therapeutic value of exercise for PD