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（由适用提供）：该提案包括高地仪器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）提供供评估该SBIR提案的唯一目的。没有其他权利获得。未经高地仪器的许可，该提案以及本文包含的商业秘密以及本文包含的其他专有或机密信息将不得全部或部分披露。如果NIH从另一个来源获得而无需限制，则该限制并不限制使用数据中包含的信息的权利。该传说适用于整个建议，包括但不限于抽象介绍，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。膝盖的OA是慢性疼痛和残疾的主要原因[1]。常规治疗并不能直接解决疼痛的事实 在大脑中处理感觉[2-5]，机械关节功能障碍可以通过慢性疼痛引起的大脑运动控制中心的变化来委托[6]。非侵入性脑刺激（NIB）已成功地用于某些疾病状态的慢性疼痛治疗，在某些疾病状态下，治疗诱导的脑活动变化恢复了与慢性疼痛的感知/感觉有关的不良适应可塑性[3，5，7]。然而，最常见的NIB方法，经颅磁刺激（TMS）和经颅直流电流刺激（TDC）未能与常规疼痛治疗的临床益处显示出一致的临床益处，并且不常用于OA治疗[8，9]。据推测，这些技术的焦点，渗透和靶向控制的局限性限制了其治疗效率[10-14]。电体刺激（ESSTIM（TM））是一种改进的NIBS模态，通过将独立控制的电磁和超声波场相结合，通过在神经组织中的调谐机电偶联来焦点和增强刺激电流，从而克服了其他技术的局限性。该提案的重点是评估我们的非侵入性ESSTIM系统是否可以有效治疗慢性OA疼痛，进而改善了膝关节生物力学功能和患者生活质量（QOL）。首先，在I阶段评估拟议工作的可行性，我们将在连续5天给予16名OA患者的ESSTIM持续固定剂量，持续20分钟/天（8 Sham Esstim，8个ESSTIM）。我们将评估患者的一系列安全性，疼痛，生物力学的膝关节功能和QOL测量，并在上次治疗后至少六个星期进行评估。第二阶段的接下来，我们将在为期两周的时间内给予64例OA患者10天，每天20天，每天20分钟。患者将随机分配到4种刺激条件中的1个：ESSTIM，TDCS，经颅超声（TUS）或假手术。我们将通过在第一阶段研究中验证的疼痛，生物力学，QOL和安全措施的疼痛，生物力学，QOL和安全措施评估这些患者，并在上一次治疗后至少八周进行了测试干预措施的效率。此外，我们将测试是否可以通过基线疾病状态来指导埃斯蒂姆疼痛抑制。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，以预测临床结果并确定最佳响应者。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ESTIM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，并进一步推进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