Noninvasive Brain Stimulation for Treating Addiction

专有：本建议书包括高地仪器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)用于评估本SBIR建议书的目的。不授予任何其他权利。这项建议和 未经高地文书许可，不得在NIH以外的地方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。这一限制不限制NIH使用数据中包含的信息的权利，如果该信息是从 另一个不受限制的来源。本图例适用于本提案的摘要、具体目标、研究计划(所有组成部分)、商业化计划和人类主题部分。 抽象的。美国正在经历一场全国性的阿片成瘾危机。虽然阿片类药物治疗是一种支柱 治疗中重度疼痛的方法；在慢性疼痛(CP)人群中，21%-29%的人滥用 处方鸦片类药物中，8%-12%发展为阿片类药物相关障碍，4%-6%转变为海洛因[1-3]。瘾君子 表现出异常的大脑网络状态，可以通过适当的治疗来改变这种状态，以减少上瘾 行为[1，2]。最近的研究表明，无创脑刺激(NIB)可能是有效的 在治疗某些形式的成瘾方面[3-10]。然而，最常见的NIBS方法，如经颅 磁刺激(TMS)和经颅直流电刺激(TDC)尚未被发现 有效治疗阿片使用障碍(OUD)([3，4])。据推测，这些方面的限制 技术的焦点、穿透性和靶向控制限制了其治疗效果[11-15]。电声 刺激(ESSTim™)是一种改进的NIBS模式，它通过结合 独立控制的电磁场和超声场，通过调谐聚焦和增强刺激电流 神经组织中的机电耦合[16，17]。这项建议的重点是评估我们的 非侵入性ESSTim系统可以有效地减少CP继发阿片类药物患者的OUD。第一 在第一阶段，为了评估拟议工作的可行性，我们将跟踪26名患者在给予固定的 连续给药5天，20分钟/天(活动组13例，假手术组13例)。我们将管理一系列 这些患者的临床/安全性、药物使用、电生理、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估。下一位是 第二阶段，我们将跟踪60名患者(30名活动患者，30名假患者)，在给予固定剂量的刺激10次后 天，每天20分钟。我们将对这些患者进行评估，评估结果与第一阶段验证的评估结果相同， 但现在将在最后一次治疗后至少12周进行评估。与...并行 在治疗过程中，我们将建立患者头部刺激场(电刺激)的MRI衍生模型 和声场模型)来计算脑目标位置处的刺激场特性。多变量 然后将建立和评估线性回归模型和广义线性回归模型来预测患者结果 作为基线疾病特征和基于MRI的剂量模型的函数。结果来自于 计算工作将被用来开发一个优化的OUD ESSTim治疗剂量模型。总体而言，我们 假设拟议的实验、计算研究和技术发展将使我们 优化ESSTim™治疗慢性阻塞性肺疾病继发于慢性阻塞性肺疾病的疗效，为改善 美国对吸毒者和成瘾者的治疗。

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.