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: 10480074
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480074
• 关键词: Aftercare; Applications Grants; Authorization documentation; Balance training; Biomechanics; Bradykinesia; Brain; California; Characteristics; Cognitive; Confidential Information; Coupled; Coupling; Data; Dependence; Development; Devices; Disease; Dose; Double-Blind Method; Electroencephalography; Electromagnetics; Electrophysiology (science); Equilibrium; Exercise; Future; Gait; Levodopa; Linear Regressions; Magnetic Resonance Imaging; Medical; Methodology; Methods; Modality; Modeling; Motor Cortex; Movement Disorder Society Unified Parkinson' s Disease Rating Scale; Multicenter Studies; Musculoskeletal Equilibrium; Neurologic; Operative Surgical Procedures; Outcome; Outcome Study; Parkinson Disease; Patients; Penetration; Pharmaceutical Preparations; Pharmacology; Phase; Physical therapy; Placebo Control; Posture; Quality of life; Questionnaires; Randomized; Regimen; Research; Rights; Safety; Short-Term Memory; Small Business Innovation Research Grant; Sonication; Source; Symptoms; Techniques; Technology; Testing; Therapeutic; Therapeutic Effect; Tissues; Training; Transcranial magnetic stimulation; Transducers; Translating; Treatment Efficacy; Ultrasonics; United States National Institutes of Health; Visit; Walking; Work; base; biomechanical test; clinically significant; commercialization; computer studies; computerized; design; disability; effectiveness testing; experimental study; follow-up; human subject; improved; instrument; interest; mortality; noninvasive brain stimulation; outcome prediction; overtreatment; posture instability; predict clinical outcome; relating to nervous system; safety assessment; sensor; side effect; technology development; therapy outcome; treatment optimization

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：本提案包括 Highland Instruments 的商业秘密和其他专有或机密信息，仅供美国国立卫生研究院 (NIH) 使用，其唯一目的是评估本 SBIR 提案，不授予本提案任何其他权利。 未经 Highland Instrument 许可，不得将本文中包含的商业秘密和其他专有或机密信息全部或部分披露给 NIH。此限制并不限制 NIH 使用从数据中获得的信息的权利。 该图例适用于整个提案，包括但不限于该提案的摘要、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。 抽象的 在帕金森病 (PD) 患者中，姿势不稳定是导致残疾、依赖身体的主要原因 目前帕金森病的治疗方法，包括药物和手术方法，都有限。 物理治疗 (PT) 越来越多地被用作治疗 PD 的一种手段。 诱导运动依赖性可塑性，可为患者平衡带来显着益处。 仍然没有针对每个患者的需求进行定制，也没有经过优化以与其他疗法协同工作 近年来，人们对使用无创脑刺激（NIBS）越来越感兴趣。 但最终，治疗 PD 的设备及其与 PT 疗法相结合的能力。 传统的 NIBS 方法对 PD 症状的影响很小且不一致，特别是 据推测，这些技术在聚焦性、穿透性和靶向性方面存在局限性。 电声刺激 (ESStim™) 是一种改进的 NIBS。 通过结合独立控制来克服其他技术的局限性的模式 电磁场和超声波场通过调谐机电来聚焦和增强刺激电流 该提案的重点是评估 ESStim 对 PD 的治疗影响。 首先，我们将跟踪 18 名 PD 患者（9 名 SHAM ESStim，9 名活跃患者）作为 PT 的辅助治疗。 ESStim）在给予固定剂量的 ESStim 刺激 10 天（每天 20 分钟）超过两年后接受 PT 我们将评估一系列电生理学、认知和神经安全标记； 平衡；生活质量（QOL）测试；统一帕金森病评定量表（UPDRS）和传感器； 两周内运动迟缓、姿势和步行能力/步态测试期间基于生物力学指标的数据 在最后一次治疗后的至少六周内，我们将在第二阶段进行 40 PD 治疗。 提供治疗一个多月后（即增加 治疗后 2 周），并按上述方式评估患者，但现在要在治疗结束后至少 8 周。 最后，我们将测试 ESStim 增强 PT 训练对 PD 姿势不稳定的效果是否可以 为了测试这一点，我们将建立并以基线疾病状态和有效刺激剂量为指导。 我们将评估多元线性和广义线性回归模型来预测临床结果。 还建立了 MRI 衍生的大脑场刺激模型（电场和声场模型） 总体而言，我们将刺激场特征与治疗结果相关联。 拟议的实验、计算研究和技术开发将使我们能够 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 结合用于 PD 治疗的方法。