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: 10601192
• 负责人: Ali R Rezai
• 金额: $ 191.84万
• 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/10601192
• 关键词: Basal Ganglia; Behavior; Brain; Brain region; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical Trials; Combined Modality Therapy; Data; Deep Brain Stimulation; Devices; Dopamine; Elements; Evaluation; Goals; Gold; 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; cohesion; 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.

摘要： 随着阿片类药物流行造成的全国死亡人数继续恶化，西弗吉尼亚州在全国领先 在过量死亡方面，每10万人中有52人死亡，以及 西弗吉尼亚州的阿片类药物流行估计约为10亿美元。阿片类药物的影响 疫情不仅限于西弗吉尼亚州；在全国范围内，超过6.3万人死于服药过量 在2016年。不幸的是，尽管治疗阿片类药物使用障碍的必要性越来越大 (OUD)，大多数患者对当前的护理标准没有反应。手术的成功率 患者最初稳定在治疗的黄金标准上，药物辅助治疗 (MAT)与心理社会干预相结合，目前不到50%。失败者 黄金标准有很高的服药过量或其他并发症的风险。由于不断增长的 以及目前治疗的局限性，显然新的治疗方法是必要的 面对这一问题，需要有各种选择。脑深部刺激(DBS)已被用于 多年来成功地治疗了帕金森氏症等运动障碍，并显示出 在其他精神障碍的研究方面很有希望。我们假设植入星展银行 大脑伏隔核区的装置将自我调节奖赏和行为 监管网络，这将减少阿片类药物的渴望。这项提案旨在测试安全性， 在UG3阶段的4名参与者的初始队列中的可行性和耐受性。这将是 允许对接受难治性治疗的参与者进行DBS的安全性和耐受性评估 OUD和继发于阿片类药物使用的危及生命的并发症史。如果UG3阶段 在对4名参与者进行密集监测后，UH3阶段将包括 随机对照概念验证研究，共有16名参与者。这些参与者将再次 有难治性尿毒症和继发性危及生命的并发症病史 阿片类药物的使用。在UH3阶段，将研究DBS对OUD的影响机理 通过神经成像和执行功能测量。