Dose-Response Effects of Whole Body Vibration on Spasticity and Walking in SCI

描述（由申请人提供）：脊髓损伤（SCI）患者经历不受控制的不随意肌肉收缩（痉挛），扰乱活动，睡眠和舒适度。痉挛是典型的药物治疗，有无数的副作用。脊髓损伤更明显的后果是随意肌控制受损，其中行走功能的限制是最具破坏性的后果之一。许多临床试验试图解决这些问题，然而，迄今为止还没有研究采取系统的方法，包括在干预之前以药物试验的方式确定剂量-反应关系。人们早就知道，振动形式的传入输入对神经回路有强大的影响；全身振动（WBV）代表了这种传入输入的强烈和广义形式。我们实验室的初步研究表明，WBV形式的传入输入可以减轻痉挛，改善步行和脊髓损伤患者。我们的发现与WBV对痉挛的影响有关，这一发现得到了长期研究的支持，这些研究表明局部振动激活了调节机制。我们实验室最近的研究表明，局部振动引起非自愿的步状行为，甚至在运动完全性脊髓损伤患者中也是如此。我们实验室之前的大部分工作都集中在使用传入输入，通常结合重复性任务练习，以促进脊髓损伤患者的神经可塑性和改善运动功能。然而，我们从来没有确定我们使用的传入输入的剂量（或练习的剂量）是最佳的。这是困扰康复研究的一个普遍问题。在进行更大规模的试验之前，需要确定剂量。显然需要以药物试验的方式逐步开展康复研究。因此，拟议的研究是一个两阶段的概念发展试验，旨在评估剂量-反应效应，确定最合适的结果测量，并选择干预的最佳组成部分。本研究将通过关注以下目标，提供与WBV对痉挛、行走功能、疼痛和肌肉力量的剂量效应相关的答案：（1期；1 - 2年）量化5种不同WBV剂量（4剂，加安慰剂）间隔1周给药的早期和晚期对痉挛和行走功能的影响。具体目标2。量化每日1次（1xWBV）和每日2次（2xWBV）的累积和持续给药对痉挛的影响，以减少痉挛最有效的剂量。具体目标3（第2阶段；第3 - 5年）。量化在最有效剂量下1xWBV与2xWBV对行走功能的累积和持续剂量效应。具体目标4（第2阶段；第3 - 5年）。描述1xWBV与2xWBV在最有效剂量下对疼痛和腿部力量的累积和持续剂量效应。

DESCRIPTION (provided by applicant): People with spinal cord injury (SCI) experience uncontrolled involuntary muscle contractions (spasticity) that disrupt mobility, sleep, and comfort. Spasticity is typically treated pharmacologically, with myriad side effects. A more obvious consequence of SCI is impaired voluntary muscle control, of which limitations of walking function are one of the most devastating consequences. Numerous clinical trials have attempted to address these issues, however, to date no studies have undertaken a systematic approach that involves identify dose-response relationships, in the manner of pharmaceutical trials, prior to the intervention. Afferent input in the form of vibration has long been known to have a powerful effect on neural circuits; whole body vibration (WBV) represents an intense and generalized form of this afferent input. Preliminary studies from our lab suggest that afferent input in the form WBV may reduce spasticity improve walking and persons with SCI. Our findings related to the influence of WBV on spasticity are supported by a long history of studies showing that local vibration activates modulatory mechanisms. Recent studies from our lab have shown that local vibration elicits involuntary step-like behavior, even in persons with motor-complete SCI. Much of the prior work of our lab has centered on the use of afferent input, often combined with repetitive task practice, to promote neuroplasticity and improved motor function in persons with SCI. However, we have never been sure that the dose of afferent input (or the dose of practice) we used was optimal. This is a common problem that plagues rehabilitation research. Questions of dose are needed before progressing to larger trials. There is a clear need for rehabilitation research studies that are developed in progressive stages in the manner of pharmaceutical trials. Accordingly, the proposed study is a 2-Phase development-of-concept trial intended to evaluate dose-response effects, identify the most suitable outcome measures, and select optimal components of the intervention. This study will provide answers related to dose effects of WBV on spasticity, walking function, pain, and muscle strength by focusing on the following Aims: Specific Aim 1. (Phase 1; Years 1 - 2) Quantify early and late within-session effects on spasticity and walking function of 5 different WBV doses (4 doses, plus placebo) delivered 1 week apart. Specific Aim 2. Quantify the cumulative and persistent dosing effects on spasticity of once daily (1xWBV) versus twice daily (2xWBV) WBV at the dose most effective for reducing spasticity. Specific Aim 3 (Phase 2; Years 3 - 5). Quantify the cumulative and persistent dosing effects on walking function of 1xWBV versus 2xWBV at the most effective dose. Specific Aim 4 (Phase 2; Years 3 - 5). Characterize the cumulative and persistent dosing effects on pain and leg strength of 1xWBV versus 2xWBV at the most effective dose.