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: 9788385
• 负责人: Ali R Rezai
• 金额: $ 37.5万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788385
• 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; Pharmaceutical Preparations; Phase; Population; Positron-Emission Tomography; Prefrontal Cortex; Raclopride; Randomized; Randomized Controlled Trials; 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; mortality; mortality risk; neurobehavioral; neuroimaging; novel; opioid epidemic; opioid misuse; opioid use; opioid use disorder; overdose death; overdose risk; procedure cost; prospective; psychosocial; 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病的全国性死亡人数继续恶化，西弗吉尼亚州在全国领先 过量死亡，每10万人中有52人死亡， 西弗吉尼亚州的阿片类药物流行病估计约为10亿美元。阿片类药物的影响 流行病不仅限于西弗吉尼亚州;在全国范围内，超过63，000人死于过量用药 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。的成功率 患者最初稳定在治疗的金标准，药物辅助治疗， (MAT)结合心理社会干预，目前不到50%。不合格者 金标准药物过量或其他并发症的风险很高。由于越来越 OUD患者的数量和目前治疗的局限性，很明显，新的治疗方法 需要采取各种办法来应对这一问题。脑深部电刺激（DBS）已被用于 多年来成功地治疗运动障碍，如帕金森氏症，并已显示 在其他精神疾病的调查中的承诺。我们假设植入DBS 在大脑的丘脑核区域的装置将调节奖励和行为自我， 监管网络，这将减少阿片类药物的渴望。该提案旨在测试安全性， 在UG 3期期间，在4名参与者的初始队列中的可行性和耐受性。这将 允许在治疗难治性受试者中评价DBS的安全性和耐受性 OUD和继发于阿片类药物使用的危及生命的并发症史。如果UG 3阶段 在对4名参与者进行密集监测后，UH 3阶段将包括： 一项随机、对照的概念验证研究，共有16名参与者。这些参与者将再次 患有难治性OUD和继发于以下疾病的危及生命的并发症史 阿片类药物使用在UH 3阶段，将研究DBS对OUD的影响机制 通过神经成像和执行功能的测量。