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：该提案包括高地工具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）提供使用该SBIR提案的唯一目的。没有其他权利获得。这个建议和 未经高地仪器的许可，不得全部或部分披露本文包含的商业秘密以及其他专有或机密信息。该限制并不限制NIH使用数据中包含的信息的权利，如果它是从数据中获得的 另一个无限制的来源。该传说适用于摘要，具体目的，研究计划（AL组件），商业化计划以及人类主题的该提案部分。 抽象的。美国正在遭受阿片类药物成瘾的国家危机。阿片类药物疗法是支柱 治疗中度至严重疼痛的方法；在慢性疼痛（CP）人群中，MISSUSE 21-29％ 规定的optiaties，8-12％的患者患有阿片类药物相关疾病，向海洛因转变为4-6％[1-3]。吸毒者 暴露的异常大脑网络状态，可以通过适当的疗法修改以减少添加剂 行为[1，2]。最近的研究表明，非侵入性大脑刺激（NIB）可能是有效的 在治疗某些形式的成瘾[3-10]中。但是，最常见的笔尖方法，例如经颅 尚未发现磁刺激（TMS）和经颅直流电流刺激（TDC） 有效治疗阿片类药物使用障碍（OUD）（[3，4]）。有人认为这些限制 技术的焦点，渗透和靶向控制限制了其治疗效率[11-15]。电气 刺激（ESSTIM™）是一种改进的NIBS模态，通过合并来克服这些限制 独立控制的电磁和超声波场，通过调谐聚焦并增强刺激电流 神经组织中的机电耦合[16，17]。该提案的重点是评估我们的 在开发于CP的患者处方的患者中，无创的Esstim系统可以有效地减少OUD。第一的 在第一阶段，为了评估拟议工作的可行性，我们将在给出固定的26名OUD患者 连续5天，20分钟/天（13个活跃，13假）剂量。我们将管理一个电池 OUD患者的临床/安全性，药物使用，电生理学，行为和社会心理评估， 在治疗期间进行评估，并在上次治疗后至少四个星期进行评估。下一个 第二阶段，我们将在给出固定剂量刺激后的60名OUD患者（30个活跃，30个假）。 天，20分钟/天。我们将通过在第一阶段验证的相同评估的相同电池评估这些患者， 但是现在评估将在上次治疗后至少十二周进行。并联 OUD治疗方法，我们将在患者头部建立刺激场的MRI衍生模型（电气 和声场模型）计算大脑目标部位的刺激场特征。多变量 然后将建立和评估线性和广义线性回归模型，以预测患者的结果 作为基线疾病特征和基于MRI的剂量模型的函数。来自 计算工作将用于开发优化的OUD ESSTIM治疗剂量模型。总体而言，我们 假设拟议的实验，计算研究和技术开发将使我们 优化ESSTIM™以治疗CP继发的OUD，并将作为改进的基础 在美国的OUD和成瘾的治疗。