Noninvasive brain stimulation for pain suppression

用于抑制疼痛的无创脑刺激

• 批准号: 9300835
• 负责人: Timothy Andrew Wagner
• 金额: $ 74.96万
• 依托单位: HIGHLAND INSTRUMENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9300835
• 关键词: Address; Aftercare; Alternative Therapies; Articular Range of Motion; Authorization documentation; Biomechanics; Brain; Characteristics; Chronic; Clinical; Clinical Research; Confidential Information; Coupling; Data; Degenerative polyarthritis; Development; Disease; Dose; Double-Blind Method; Effectiveness; Electroencephalography; Electromagnetics; Electrophysiology (science); Equilibrium; Esthesia; Feasibility Studies; Functional disorder; Future; Gait; Intervention; Joints; Knee; Knee Osteoarthritis; Length; Linear Regressions; Measurement; Measures; Mechanics; Medical; Methods; Modality; Modeling; Motor Cortex; Multicenter Studies; Neurologic; Nociception; Outcome; Outcome Study; Pain; Pain management; Patients; Pattern; Penetration; Perception; Phase; Placebo Control; Placebos; Process; Quality of life; Randomized; Research; Rights; Safety; Sensory; Small Business Innovation Research Grant; Source; Speed; Symptoms; System; Techniques; Technology; Testing; Therapeutic; Tissues; Transcranial magnetic stimulation; Treatment Efficacy; Ultrasonics; Ultrasonography; United States National Institutes of Health; Western Ontario and McMaster Universities Arthritis Index; Work; chronic pain; commercialization; comparative efficacy; computer studies; conventional therapy; disability; efficacy testing; experimental study; human subject; improved; indexing; instrument; knee pain; motor control; outcome prediction; permissiveness; phase 1 study; phase 2 study; predict clinical outcome; public health relevance; relating to nervous system; technology development; treatment duration; trial design

 DESCRIPTION (provided by applicant): 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. OA of the knee is a leading cause of chronic pain and disability [1]. Conventional treatments do not directly address the fact that pain sensation is processed in the brain [2-5] and mechanical joint dysfunction can be worsened by chronic pain induced changes in the brain's motor control centers [6]. Non-Invasive Brain Stimulation (NIBS) has been successfully applied for the treatment of chronic pain in some disease states, where treatment induced changes in brain activity revert maladaptive plasticity associated with the perception/sensation of chronic pain [3, 5, 7]. However the most common NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), fail to show consistent clinical benefit on par with that of the conventional pain treatments and are not commonly used for OA therapy [8, 9]. It has been postulated that limitations in these techniques' focality, penetration, and targeting control limit their therapeutc efficacy [10-14]. Electrosonic Stimulation (ESStim(tm)) 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 whether our noninvasive ESStim system can effectively treat chronic OA pain, and in turn improve knee biomechanical function and patient quality of life (QOL). First in Phase I to assess the feasibilit of the proposed work, we will follow 16 OA patients after giving a constant fixed dose of ESStim for 20 min/day on 5 consecutive days (8 SHAM ESStim, 8 ESStim). We will assess a battery of safety, pain, biomechanical knee function, and QOL measures in the patients, evaluated over the treatment period and for at least six weeks following the last treatment session. Next in Phase II, we will follow 64 OA patients after giving a constant fixed dose of stimulation for 10 days, 20 min/day, over a two-week period. Patients will randomly be assigned to 1 of 4 stimulation conditions: ESStim, tDCS, transcranial ultrasound (TUS), or SHAM ESStim. We will evaluate these patients with the battery of pain, biomechanical, QOL, and safety measures, which were validated in the Phase I studies, and compare the efficacy of the tested interventions for at least eight weeks following the last treatment session. Furthermore, we will test whether the ESStim pain suppression can be guided by the baseline disease state. To test this we will build and evaluate multivariate linear and generalized linear regression models to predict the clinical outcomes and identify best responders. Overall, we hypothesize that the proposed experiments, computational studies, and technology development will allow us to test the effectiveness of ESStim in OA patients. The work will serve as the basis for a future large-scale multicenter study and further the commercialization of ESStim OA therapy.

 描述(由申请人提供)：本建议书包括商业秘密和高地仪器的其他专有或机密信息，由美国国立卫生研究院(NIH)提供，仅用于评估本SBIR建议书。不授予任何其他权利。未经高地文书许可，不得在NIH以外的地方披露本提案以及本文中包含的商业秘密和其他专有或机密信息的全部或部分。这一限制并不限制NIH使用数据中包含的信息的权利，如果这些信息是从其他来源获得的，而不受限制。这一图例适用于整个提案，包括但不限于本提案的摘要介绍、具体目标、研究计划(所有组成部分)、商业化计划和人类主体部分。抽象的。膝关节骨关节炎是慢性疼痛和残疾的主要原因[1]。传统的治疗方法并不能直接解决这样一个事实 感觉是在大脑中处理的[2-5]，慢性疼痛引起的大脑运动控制中心的变化会加重机械性关节功能障碍[6]。非侵入性脑刺激(NIBS)已经成功地应用于某些疾病状态下的慢性疼痛的治疗，治疗引起的脑活动的变化逆转了与慢性疼痛的知觉/感觉相关的适应不良可塑性[3，5，7]。然而，最常见的NIBS方法，经颅磁刺激(TMS)和经颅直流电刺激(TDCS)，未能显示出与传统疼痛治疗相同的一致的临床益处，也不常用于骨关节炎治疗[8，9]。据推测，这些技术在焦点、穿透和靶向控制方面的局限性限制了它们的治疗效果[10-14]。电声刺激(ESSTim(Tm))是一种改进的NIBS模式，它通过将独立控制的电磁场和超声场相结合，通过神经组织中可调的机电耦合来聚焦和增强刺激电流，从而克服了其他技术的局限性。这项建议的重点是评估我们的非侵入性ESSTim系统是否可以有效地治疗慢性骨性关节炎疼痛，进而改善膝关节生物力学功能和患者的生活质量(QOL)。首先，在评估拟议工作的可行性的第一阶段，我们将跟踪16名OA患者，在连续5天给予固定剂量的ESSTim 20分钟/天(8个假ESSTim，8个ESSTim)。我们将评估患者的一系列安全性、疼痛、生物力学膝关节功能和生活质量指标，并在治疗期间和最后一次治疗后至少六周进行评估。接下来，在第二阶段，我们将跟踪观察骨性关节炎患者，在两周内给予固定剂量的恒定刺激10天，20分钟/天。患者将被随机分配到4种刺激条件中的一种：ESSTim、TDCS、经颅超声(TUS)或假ESSTim。我们将对这些患者进行疼痛、生物力学、生活质量和安全措施的评估，这些措施在I期研究中得到验证，并在最后一次治疗后至少八周内比较测试的干预措施的有效性。此外，我们将测试ESSTim疼痛抑制是否可以根据基线疾病状态进行指导。为了测试这一点，我们将建立和评估多变量线性回归模型和广义线性回归模型，以预测临床结果并确定最佳应答者。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能够测试ESSTim在OA患者中的有效性。这项工作将作为未来大规模多中心研究的基础，并进一步推动ESSTim OA疗法的商业化。

项目成果

Cost-Effectiveness Analysis to Inform Randomized Controlled Trial Design in Chronic Pain Research: Methods for Guiding Decisions on the Addition of a Run-In Period.

成本效益分析为慢性疼痛研究中的随机对照试验设计提供信息：指导决定增加磨合期的方法。

• DOI: 10.21801/ppcrj.2022.82.5
• 发表时间: 2022
• 期刊: Principles and practice of clinical research (2015)
• 作者: Rafferty,Haley;Rocha,Elisa;Gonzalez-Mego,Paola;Ramos,ClaraL;El-Hagrassy,MirretM;Gunduz,MuhammedE;Uygur-Kucukseymen,Elif;Zehry,Hanan;Chaudhari,SwapnaliS;Teixeira,PauloEp;Rosa,GleyssonR;Zaninotto,AnaL;Connor,Christopher;Eden
• 通讯作者: Eden