Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory Opioid Use Disorder

深部脑刺激作为难治性阿片类药物使用障碍新疗法的可行性

• 批准号: 10823599
• 负责人: Ali R Rezai
• 金额: $ 28.64万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10823599
• 关键词: Abstinence; Acute; Address; Applications Grants; Bilateral; Brain; Caring; Categories; Communities; Cues; Data; Data Set; Death Rate; Deep Brain Stimulation; Devices; Dose; Enrollment; Epidemic; Evaluation; FDA approved; Focused Ultrasound; Focused Ultrasound Therapy; Functional Magnetic Resonance Imaging; Funding; Future; Generations; Goals; Government; Grant; Health; Individual; Methamphetamine; Methodology; Modality; Nucleus Accumbens; Operative Surgical Procedures; Opioid; Outcome; Outcome Assessment; Parents; Participant; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Prevalence; Procedures; Protocols documentation; Recording of previous events; Refractory; Relapse; Research Personnel; Resources; Rest; Rewards; Safety; Sampling; Sonication; Structure; Substance Use Disorder; Suggestion; Testing; Therapeutic; Toxicology; Transcranial magnetic stimulation; Urine; West Virginia; addiction; cognitive function; cohort; craving; cue reactivity; emotional symptom; executive function; follow-up; frontal lobe function; implantation; improved; improved outcome; medical complication; medication for opioid use disorder; mortality; neural circuit; neuroregulation; novel; opioid use; opioid use disorder; overdose death; parent grant; participant enrollment; polysubstance use; primary outcome; reduced substance use; reward circuitry; secondary endpoint; substance use

PROJECT SUMMARY The addiction epidemic continues to ravage the nation despite the scientific efforts of researchers and the funding resources provided at state and government levels. Overdose deaths this year, most of which involved opioids, were the highest in recorded history. While medication for opioid use disorder (MOUD) has been effective in improving outcomes, approximately 50% of those seeking treatment subsequently relapse on opioids and/or other substances. Further complicating matters, the prevalence of substance use disorders (SUDs) co-occurring with OUD, many of which do not yet have effective medication treatments available (e.g., methamphetamine), suggests that this epidemic extends well beyond opioids. As such, new treatment modalities are urgently needed to address the addiction epidemic plaguing our communities. Various forms of neuromodulation have demonstrated promising results as a potential adjunctive treatment to the standard level of care for SUD; however, these forms of neuromodulation are not without their limitations. Noninvasive forms are unable to precisely target subcortical structures integral to the addiction/reward circuitry, such as the nucleus accumbens (NAc), while those capable of targeting these regions require an invasive surgery with accompanying potential complications and burden. Low Intensity Focused Ultrasound (LIFU), circumvents these limitations, demonstrating the capability to precisely target subcortical structures without requiring an invasive surgical procedure or device implantation. Our team recently completed a pilot study investigating LIFU in eight individuals with OUD which demonstrated that LIFU targeting the NAc, was safe and well-tolerated. Participants who received a “therapeutic” LIFU dose (90-100W; n=6) also evidenced substantial decreases in craving acutely during LIFU sonication and suggestion of prolonged reductions throughout post-LIFU Day 90 follow-up. The overarching goal of the current application is to enroll a new cohort of 5 participants with OUD for purposes of replicating and expanding the findings demonstrated in the six previously enrolled participants who received the “therapeutic” LIFU dose (resulting in a dataset with a cumulative sample of 11 participants). Co-primary outcomes include safety and cue-induced craving at the post-LIFU Day 7 endpoint with secondary endpoints extending through the post-LIFU Day 90 follow-up. Secondary/exploratory outcomes include the evaluation of NAc LIFU on substance use, functional connectivity (assessed via fMRI), emotional symptoms, cognitive functioning, and treatment engagement. We hypothesize that LIFU applied to the NAc will be safe and well- tolerated and will modulate the brain networks associated with reward and addiction, thereby reducing opioid and other substance craving and improving outcomes in individuals with OUD. An important outcome of this proposal is the generation of new information regarding the impact of LIFU as a treatment for OUD. These data will be used to develop future grant proposals to investigate, refine, and establish LIFU treatment for OUD to address this emergent health crisis that continues to grow at alarming rates.

项目概要 尽管研究人员做出了科学努力并提供了资金，成瘾流行病仍在肆虐全国 州和政府层面提供的资源。今年过量死亡，其中大部分涉及阿片类药物， 是有记录以来的最高水平。虽然治疗阿片类药物使用障碍 (MOUD) 的药物已有效 改善结果，大约 50% 寻求治疗的患者随后在阿片类药物和/或药物治疗后复发 其他物质。使问题更加复杂的是，物质使用障碍 (SUD) 的流行同时发生 OUD，其中许多尚无有效的药物治疗（例如甲基苯丙胺）， 表明这种流行病的范围远远超出了阿片类药物的范围。因此，迫切需要新的治疗方式 解决困扰我们社区的毒瘾流行问题。各种形式的神经调节 作为 SUD 标准护理水平的潜在辅助治疗，显示出有希望的结果； 然而，这些形式的神经调节并非没有局限性。非侵入性形式无法 精确瞄准成瘾/奖励回路不可或缺的皮质下结构，例如伏隔核 （NAc），而那些能够针对这些区域的人需要进行侵入性手术，并伴随潜在的 并发症和负担。低强度聚焦超声 (LIFU) 规避了这些限制， 展示无需侵入性手术即可精确瞄准皮质下结构的能力 程序或装置植入。我们的团队最近完成了一项试点研究，调查 LIFU 在八个领域的应用 患有 OUD 的个体表明，针对 NAc 的 LIFU 是安全且耐受性良好的。参加者 接受“治疗”LIFU 剂量（90-100W；n=6）的人也表现出强烈的渴望大幅减少 在 LIFU 超声处理期间，建议在 LIFU 后第 90 天的随访期间延长减少量。这 当前申请的总体目标是通过 OUD 招募 5 名新参与者，以便 复制并扩展了先前注册的六名接受过治疗的参与者所展示的研究结果 “治疗”LIFU 剂量（产生包含 11 名参与者的累积样本的数据集）。联合小学 结果包括 LIFU 后第 7 天终点的安全性和提示诱发的渴望以及次要终点 延续到 LIFU 第 90 天后的随访。次要/探索性结果包括评估 NAc LIFU 关于物质使用、功能连接（通过功能磁共振成像评估）、情绪症状、认知 功能和治疗参与度。我们假设 LIFU 应用于 NAc 将是安全且良好的- 耐受性并将调节与奖励和成瘾相关的大脑网络，从而减少阿片类药物 和其他物质渴望并改善 OUD 患者的结果。此次活动的一个重要成果 该提案的目的是生成有关 LIFU 作为 OUD 治疗方法的影响的新信息。这些数据 将用于制定未来的拨款提案，以调查、完善和建立 OUD 的 LIFU 治疗方法 解决这一持续以惊人速度增长的突发健康危机。