Enhancing Physical Therapy with Brain Stimulation for Treating Postural Instability

通过脑刺激加强物理治疗治疗姿势不稳定

• 批准号: 10457547
• 负责人: Laura Dipietro
• 金额: $ 74.99万
• 依托单位: HIGHLAND INSTRUMENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457547
• 关键词: Enhancing; Physical; Therapy; Brain; Stimulation

Proprietary: This proposal includes trade secrets and other proprietary or confidential information of Highland Instruments and is being provided for use by the National Institutes of Health (NIH) for the sole purpose of evaluating this SBIR proposal. No other rights are conferred. This proposal and the trade secrets and other proprietary or confidential information contained herein shall further not be disclosed in whole or in parts, outside of NIH without Highland Instrument's permission. This restriction does not limit the NIH's right to use information contained in the data if it is obtained from another source without restriction. This legend applies to the entire proposal, including, but not limited to the Abstract, Introduction, Specific Aims, Research Plan (all components), Commercialization Plan, and Human Subject's Sections of this proposal. Abstract In patients with Parkinson’s Disease (PD), postural instability is a leading cause of disability, dependence on others, and mortality. Current treatments for PD, including pharmacological and surgical methods, have limited impact on postural instability. Physical therapy (PT) for PD is becoming increasingly used as a means to induce exercise-dependent plasticity that can result in significant benefits for patient balance. However, PT is still untailored to each patient need, and has not been optimized to work synergistically with other therapies in PD. In recent years, there has been an increased interest in the use of noninvasive brain stimulation (NIBS) devices for the treatment of PD and in their ability to couple their effects with PT regimens. But, ultimately conventional NIBS methods have showed minimal and inconsistent effects on PD symptoms, and in particular patient balance. It has been postulated that these techniques’ limitations in focality, penetration, and targeting control translate into their limited therapeutic effects. Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes the limitations of other technologies by combining independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue. This proposal is focused on evaluating the therapeutic impact of ESStim in PD patients as adjunct therapy to PT. First in Phase I, we will follow 18 PD patients (9 SHAM ESStim, 9 active ESStim) undergoing PT after giving a fixed dose of ESStim for 10 days of stimulation, 20 mins/day, over a two- week period. We will assess a battery of electrophysiology, cognitive, and neurological safety markers; balance; Quality of Life (QOL) tests; the Unified Parkinson’s Disease Rating Scale (UPDRS); and sensor- based, biomechanical metrics during bradykinesia, posture, and walking abilities/gait tests over the 2-week period and for at least six weeks following the last treatment session. Next in Phase II, we will follow 40 PD patients (20 SHAM, 20 active ESStim stimulation) after providing treatment over a month (i.e., increasing treatment by 2 weeks), and assess the patients as above, but now for at least 8 weeks after treatment ends. Finally, we will test whether the effects of ESStim enhanced PT training for postural instability in PD can be guided by the baseline disease state and the effective dose of stimulation. To test this we will build and evaluate multivariate linear and generalized linear regression models to predict the clinical outcomes. We will also build MRI derived models of the stimulation fields in the brain (electrical and sonic field models) of each of the PD subjects and correlate the stimulatory field characteristics with therapeutic outcomes. Overall, we hypothesize that the proposed experiments, computational studies, and technology development will allow us to test the effectiveness of ESStim as adjunct therapy to PT in PD patients. The results of the proposed work will serve as the basis for a future large-scale multicenter study to further validate the technique and optimize the methodology of ESStim coupled with PT for use in PD therapy.

专有：本提案包含Highland Instruments的商业机密和其他专有或机密信息，仅供美国国立卫生研究院（NIH）用于评估本SBIR提案。不授予其他权利。这一建议和 未经Highland Instrument的许可，不得在NIH之外披露本文所含的商业秘密和其他专有或机密信息的全部或部分内容。这一限制并不限制NIH使用数据中包含的信息的权利，如果这些信息是从以下来源获得的： 另一个来源没有限制。本图例适用于整个提案，包括但不限于本提案的摘要、引言、具体目标、研究计划（所有组成部分）、商业化计划和人类受试者部分。 摘要 在帕金森病（PD）患者中，姿势不稳定是残疾的主要原因，依赖于 其他人和死亡率。目前的PD治疗，包括药物和手术方法， 对姿势不稳定的影响。PD的物理治疗（PT）越来越多地被用作一种手段， 诱导运动依赖性可塑性，其可导致对患者平衡的显著益处。然而，PT 仍然不适合每个患者的需要，并且尚未优化以与其他疗法协同工作， 警局近年来，人们对无创脑刺激（NIBS）的使用越来越感兴趣 治疗PD的器械及其与PT方案相结合的能力。但最终 常规NIBS方法对PD症状的影响极小且不一致，特别是 患者平衡据推测，这些技术在聚焦、穿透和靶向方面的局限性 控制转化为有限的治疗效果。电声刺激（ESStim™）是一种改进的NIBS 通过结合独立控制的技术，克服其他技术的局限性的模式 电磁场和超声场，以通过调谐的机电 神经组织中的耦合。该提案的重点是评估ESStim在PD中的治疗影响 患者作为PT的辅助治疗。首先在I期，我们将随访18例PD患者（9例假ESStim，9例活性 ESStim）在给予固定剂量的ESStim刺激10天后接受PT，20分钟/天，持续2- 周期间。我们将评估一组电生理学、认知和神经安全性标志物; 平衡;生活质量（QOL）测试;统一帕金森病评定量表（UMRS）;和传感器- 2周内运动迟缓、姿势和行走能力/步态测试期间的生物力学指标 期间，并在最后一次治疗后至少6周。接下来在第二阶段，我们将遵循40 PD 患者（20例假手术，20例活动ESStim刺激）在提供治疗一个月后（即，增加 治疗2周），并如上所述评估患者，但现在治疗结束后至少8周。 最后，我们将测试ESStim增强PT训练对PD姿势不稳定的影响是否可以 由基线疾病状态和有效刺激剂量指导。为了测试这一点，我们将建立和 评估多变量线性和广义线性回归模型，以预测临床结局。我们将 还建立每个人的大脑中刺激场的MRI衍生模型（电场和声场模型）， PD受试者，并将刺激场特征与治疗结果相关联。总的来说，我们 假设所提出的实验、计算研究和技术发展将使我们能够 测试ESStim作为PD患者PT辅助治疗的有效性。拟议工作的结果 将作为未来大规模多中心研究的基础，以进一步验证该技术并优化 ESStim与PT联合用于PD治疗的方法学。