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：该提案包括高地工具的商业秘密和其他专有或机密信息，并正在美国国立卫生研究院（NIH）提供使用该SBIR提案的唯一目的。没有其他权利获得。这个建议和 未经高地仪器的许可，不得全部或部分披露本文包含的商业秘密以及其他专有或机密信息。该限制并不限制NIH使用数据中包含的信息的权利，如果它是从数据中获得的 另一个无限制的来源。该传说适用于整个建议，包括但不限于摘要，引言，特定目的，研究计划（所有组件），商业化计划以及人类主题的该提案部分。 抽象的 在帕金森氏病（PD）的患者中，姿势不稳定是残疾的主要原因，依赖 其他人和死亡率。当前对PD的治疗方法，包括药物和外科手术方法有限 对姿势不稳定的影响。 PD的物理疗法（PT）越来越多地用作 诱导运动依赖性可塑性，从而为患者平衡带来重大益处。但是，pt是 仍然对每个患者需求都没有遗传，并且尚未优化以与其他疗法协同工作 PD。近年来，对使用非侵入性脑刺激（NIB）的兴趣增加了 治疗PD的设备及其将其效果与PT方案搭配的能力。但是，最终 常规的NIBS方法显示对PD症状的影响很小，尤其是不一致的影响 患者平衡。有人认为，这些技术在焦点，渗透和靶向方面的限制 控制转化为其有限的治疗作用。电刺激（ESSTIM™）是改进的笔尖 通过组合独立控制来克服其他技术的局限性的方式 电磁场和超声波场，通过调谐机电聚焦和增强刺激电流 在神经组织中耦合。该提案的重点是评估Esstim在PD中的治疗影响 患者是PT的辅助疗法。第一阶段，我们将关注18例PD患者（9个假埃斯蒂姆，9个活跃 在将PT固定剂量刺激10天之后，每天20分钟，在两个 - 两次 - 周期。我们将评估一系列电生理学，认知和神经系统安全标记； 平衡;生活质量（QOL）测试；统一的帕金森氏病评级量表（UPDRS）；和传感器 - 在2周期间，基于Bradykinesia，姿势和步行能力/步态测试期间的生物力学指标 上次治疗后至少六个星期。第二阶段，我们将关注40 PD 在一个月内提供治疗后，患者（20个假，20个主动刺激）（即增加 治疗2周），并如上所述评估患者，但现在至少在治疗后至少8周。 最后，我们将测试Esstim增强PT训练对PD中姿势不稳定的影响是否可以是 在基线疾病状态和有效刺激的指导下。为了测试这一点，我们将构建和 评估多元线性和广义线性回归模型以预测临床结果。我们将 还构建每个大脑中刺激场的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。总体而言，我们 假设拟议的实验，计算研究和技术开发将使我们 在PD患者中测试ESTIM作为PT的辅助疗法的有效性。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的方法与PT一起用于PD治疗。