Noninvasive Brain Stimulation for Treating Addiction

用于治疗成瘾的无创脑刺激

• 批准号: 10650582
• 负责人: Laura Dipietro
• 金额: $ 75万
• 依托单位: HIGHLAND INSTRUMENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10650582
• 关键词: Acoustics; Addictive Behavior; Aftercare; American; Area; Authorization documentation; Back; Behavior; Behavior assessment; Behavioral; Biophysics; Brain; Characteristics; Clinical; Clinical Research; Confidential Information; Country; Coupling; Cues; Data; Disease; Dose; Double-Blind Method; Drug Prescriptions; Drug usage; Effectiveness; Electroencephalography; Electromagnetics; Electrophysiology (science); Exhibits; Foundations; Frequencies; Head; Health; Heroin; Image; Impulsivity; Interview; Left; Linear Regressions; Magnetic Resonance Imaging; Measurement; Medical; Methods; Modality; Modeling; Movement Disorders; National Institute of Drug Abuse; Neurologic; Obsessive compulsive behavior; Opiate Addiction; Opioid; Opioid Analgesics; Opioid-Related Disorders; Outcome Study; Pain; Patient-Focused Outcomes; Patients; Penetration; Performance; Pharmaceutical Preparations; Pharmacology; Phase; Placebo Control; Population; Prefrontal Cortex; Procedures; Psychosocial Assessment and Care; Questionnaires; Randomized; Research; Rest; Rights; Risk; Safety; Secondary to; Self Assessment; Site; Small Business Innovation Research Grant; Source; Stratification; System; Techniques; Technology; Testing; Therapeutic Effect; TimeLine; Tissues; Transcranial magnetic stimulation; Treatment Efficacy; Ultrasonics; United States National Institutes of Health; Work; addiction; base; behavioral study; chronic pain; chronic pain management; chronic painful condition; clinical pain; commercialization; computer studies; cost; density; diaries; drinking; experimental study; human subject; illicit opioid; improved; instrument; metabolic abnormality assessment; noninvasive brain stimulation; novel; opioid epidemic; opioid misuse; opioid therapy; opioid use; opioid use disorder; outcome prediction; overtreatment; prescription opioid; prognostic; psychosocial; relating to nervous system; safety assessment; side effect; technology development; treatment duration; vector

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 shal 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 Abstract, Specific Aims, Research Plan (al components), Commercialization Plan, and Human Subject's Sections of this proposal. Abstract. The USA is undergoing a national crisis of opioid addiction. While opioid therapy is a mainstay approach for the treatment of moderate to severe pain; in the chronic pain (CP) population, 21-29% misuse prescribed opiates, 8-12% develop an opioid related disorder, and 4- 6% transition to heroin [1-3]. Addicts exhibit aberrant brain network states, which may be modified through appropriate therapies to reduce addictive behavior [1, 2]. Recent studies have demonstrated that noninvasive brain stimulation (NIBS) may be effective in treating some forms of addiction [3-10]. However, the most common NIBS methods, e.g., Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), have not been found to be effective in treating opioid use disorder (OUD) ([3, 4]). It has been postulated that limitations in these techniques’ focality, penetration, and targeting control limit their therapeutic efficacy [11-15]. Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes these limitations by combining independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue [16, 17]. This proposal is focused on evaluating whether our noninvasive ESStim system can effectively reduce OUD in patients prescribed opioids secondary to CP. First in Phase I, to assess the feasibility of the proposed work, we will follow 26 OUD patients after giving a fixed dose of ESStim for 5 consecutive days, 20 min/day (13 Active, 13 SHAM). We will administer a battery of clinical/safety, drug-use, electrophysiology, behavioral, and psychosocial assessments in the OUD patients, evaluated over the treatment period and for at least four weeks following the last treatment session. Next in the Phase II, we will follow 60 OUD patients (30 Active, 30 SHAM) after giving a fixed dose of stimulation for 10 days, 20 min/day. We will evaluate these patients with the same battery of assessments validated in Phase I, but now assessments will be made at least twelve weeks following the last treatment session. In parallel with the OUD treatments, we will build MRI derived models of the stimulation fields in the patients’ heads (electric and acoustic field models) to calculate the stimulation field characteristics at the brain target sites. Multivariate linear and generalized linear regression models will then be built and evaluated to predict the patient outcomes as a function of baseline disease characteristics and the MRI based dosing models. The results from the computational work will be used to develop an optimized OUD ESStim treatment dosing model. Overall, we hypothesize that the proposed experiments, computational studies, and technology development will allow us to optimize ESStim™ for treatment of OUD secondary to CP and will serve as the foundation to improve the treatment of OUD and addiction in the US.

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之外披露本文中包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。本图例适用于本提案的摘要、具体目的、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。美国正在经历一场阿片类药物成瘾的全国性危机。虽然阿片类药物治疗是 用于治疗中度至重度疼痛的方法;在慢性疼痛（CP）人群中，21-29%误用 处方阿片类药物，8-12%发展为阿片类药物相关疾病，4- 6%过渡到海洛因[1-3]。成瘾者 表现出异常的大脑网络状态，这可以通过适当的治疗来改变，以减少成瘾 行为[1，2]。最近的研究表明，无创脑刺激（NIBS）可能是有效的 治疗某些形式的成瘾[3-10]。然而，最常见的NIBS方法，例如，经颅 磁刺激（TMS）和经颅直流电刺激（tDCS）尚未被发现 有效治疗阿片类药物使用障碍（OUD）（[3，4]）。据推测，这些限制 技术的聚焦性、穿透性和靶向控制限制了其治疗效果[11-15]。Electrosonic 刺激（ESStim™）是一种改进的NIBS模式，通过结合 独立控制的电磁场和超声场，以通过调谐 神经组织中的机电耦合[16，17]。这一建议的重点是评估我们是否 非侵入性ESStim系统可有效减少继发于CP的阿片类药物患者的OUD。第一 在第一阶段，为评估建议工作的可行性，我们会在给予一个固定的 剂量的ESStim，连续5天，20分钟/天（13例活性，13例假手术）。我们会给你一系列 OUD患者的临床/安全性、药物使用、电生理学、行为和心理社会评估， 在治疗期间和最后一次治疗后至少四周内进行评价。中的下 在第二阶段，我们将在给予固定剂量的刺激10分钟后随访60名OUD患者（30名活动患者，30名假手术患者）。 20 min/d。我们将使用在I期试验中验证的相同评估组合对这些患者进行评估， 但现在将在最后一次治疗后至少12周进行评估。平行于 在OUD治疗中，我们将建立患者头部刺激场的MRI衍生模型（电 和声场模型）来计算大脑目标部位处的刺激场特性。多元 然后将建立线性和广义线性回归模型并进行评估，以预测患者结局 作为基线疾病特征和基于MRI的给药模型的函数。的结果 计算工作将用于开发优化的OUD ESStim治疗剂量模型。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 优化ESStim™治疗继发于CP的OUD，并将作为改善 在美国治疗OUD和成瘾。