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: 10697336
• 负责人: Ali R Rezai
• 金额: $ 193.46万
• 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/10697336
• 关键词: Basal Ganglia; Behavior; Brain; Brain region; Cessation of life; Clinical Trials; Combined Modality Therapy; Data; Deep Brain Stimulation; Devices; Dopamine; Elements; Evaluation; Explosion; Goals; Healthcare Systems; Implant; Implantation procedure; Individual; Informal Social Control; Institutional Review Boards; Internal Capsule; Intervention; Investigation; Leadership; Measurement; Medical; Mental disorders; Methods; Modality; Monitor; Movement Disorders; Nucleus Accumbens; Obsessive-Compulsive Disorder; Operative Surgical Procedures; Opioid; Overdose; Parkinson Disease; Participant; Patients; Persons; Pharmaceutical Preparations; Phase; Population; Positron-Emission Tomography; Prefrontal Cortex; Raclopride; Randomized; Refractory; Resources; Rewards; Safety; Secondary to; Surgeon; Titrations; Treatment outcome; United States Food and Drug Administration; West Virginia; brain pathway; cohort; craving; economic impact; executive function; experience; fluorodeoxyglucose positron emission tomography; frontal lobe; glucose metabolism; high risk; implantation; improved; improved outcome; life history; medication-assisted treatment; mortality; mortality risk; neurobehavioral; neuroimaging; novel; opioid epidemic; opioid misuse; opioid use; opioid use disorder; overdose death; overdose risk; procedure cost; prospective; psychosocial; randomized, controlled study; response; reward circuitry; safety and feasibility; safety study; safety testing; standard care; standard of care; success

Abstract: As the national toll from the opioid epidemic continues to worsen, West Virginia leads the nation in overdose deaths, with 52 deaths per 100,000 population, and the economic impact of the opioid epidemic on West Virginia is estimated at around $1 billion. The impact of the opioid epidemic is not limited to West Virginia; nationally, more than 63,000 overdose deaths occurred in 2016. Unfortunately, despite the growing necessity of treatment for Opioid Use Disorder (OUD), most patients do not respond to the current standard of care. The success rate of patients initially stabilized on the gold standard of treatment, Medication Assisted Therapy (MAT) in conjunction with psychosocial interventions, is currently less than 50%. Those who fail the gold standard have a high risk of overdose or other complications. Due to the growing number of OUD patients and the limitations of current treatment, it is clear that new treatment options are needed to confront this problem. Deep Brain Stimulation (DBS) has been used for many years to successfully treat movement disorders such as Parkinsons, and has shown promise in investigations for other mental disorders. We hypothesize that implanting the DBS device in the nucleus accumbens region of the brain will modulate the reward and behavior self- regulation networks, which will decrease opioid cravings. This proposal aims to test safety, feasibility, and tolerability in an initial cohort of 4 participants during the UG3 phase. This will allow for an evaluation of safety and tolerability of DBS in participants with treatment-refractory OUD and a history of life-threatening complications secondary to opioid use. If the UG3 phase is successful following intensive monitoring of the 4 participants, the UH3 phase will consist of a randomized, controlled proof-of-concept study with 16 participants. These participants again will have treatment-refractory OUD and a history of life-threatening complications secondary to opioid use. During the UH3 phase, the mechanism of DBS impact on OUD will be investigated through both neuroimaging and measurement of executive function.

抽象的： 随着阿片类药物流行病造成的全国死亡人数继续恶化，西弗吉尼亚州领先全国 药物过量死亡（每 10 万人中有 52 人死亡），以及药物过量造成的经济影响 西弗吉尼亚州的阿片类药物流行病估计造成约 10 亿美元的损失。阿片类药物的影响 疫情不仅限于西弗吉尼亚州；全国范围内，已有超过 63,000 人因服药过量死亡 2016 年。不幸的是，尽管治疗阿片类药物使用障碍的必要性日益增加 （OUD），大多数患者对当前的护理标准没有反应。成功率 患者最初稳定在黄金治疗标准——药物辅助治疗上 (MAT) 与心理社会干预相结合，目前不到 50%。那些失败的人 黄金标准有服用过量或其他并发症的高风险。由于日益增长 OUD 患者的数量和当前治疗的局限性，很明显新的治疗方法 需要有多种选择来应对这个问题。深部脑刺激（DBS）已被用于 多年来成功治疗帕金森等运动障碍，并已证明 对其他精神障碍的研究有希望。我们假设植入 DBS 大脑伏隔核区域的装置将自我调节奖励和行为 监管网络，这将减少对阿片类药物的渴望。该提案旨在测试安全性， UG3 阶段 4 名参与者的初始队列的可行性和耐受性。这将 允许评估难治性参与者的 DBS 安全性和耐受性 OUD 和继发于阿片类药物使用的危及生命的并发症的病史。如果UG3相 在对 4 名参与者进行密集监测后取得成功，UH3 阶段将包括 有 16 名参与者参与的随机、对照概念验证研究。这些参与者将再次 有治疗难治性 OUD 和继发于危及生命的并发症的病史 阿片类药物的使用。在UH3阶段，将研究DBS对OUD影响的机制 通过神经影像学和执行功能的测量。