Deep Brain Stimulation (DBS) For Severe Treatment Refractory Methamphetamine Use Disorder

深部脑刺激 (DBS) 治疗难治性甲基苯丙胺使用障碍

基本信息

批准号：
10630368
负责人：
AVIVA ABOSCH
金额：
$ 64.5万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10630368
关键词：
Abstinence Admission activity Affect Aftercare Alcohols American Anhedonia Animal Model Animals Anterior Area Back Behavioral Paradigm Bilateral Bioethics Consultants Biological Biological Markers Biometry Blinded Brain Case Study Cessation of life Chronic Clinic Clinical Clinical Data Clinical Trials Controlled Study Cross-Over Studies Crossover Design Cues Deep Brain Stimulation Drug Metabolic Detoxication Drug Screening Drug usage Electrophysiology (science)Enrollment Equilibrium Event Experimental Designs FDA approved Feasibility Studies Functional Magnetic Resonance Imaging Functional disorder Glutamates Human Implant Impulsivity Incidental Findings Individual Inpatients Intervention Knowledge Life Measurement Measures Medial Methamphetamine Methamphetamine use disorder Monitor Morbidity - disease rate Movement Disorders Neurology Neurons Neurosciences Neurosurgeon Nucleus Accumbens Obsessive-Compulsive Disorder Operative Surgical Procedures Opioid Outcome Patient Self-Report Persons Pharmaceutical Preparations Pharmacotherapy Phase Phenotype Physiologic pulse Placebos Play Prefrontal Cortex Procedures Psychiatrist Publishing Randomized Recording of previous events Refractory Reporting Rest Rewards Risk Taking Role Safety Signal Transduction Stimulant Stimulus Stream Structure Substance Use Disorder Synapses Technology Testing Time Treatment outcome United States Substance Abuse and Mental Health Services Administration Urine Ventral Tegmental Area addiction arm clinical outcome assessment cognitive process craving design evidence base experience improved methamphetamine use mortality neural neural circuit novel novel strategies phase 2 study preventable death prospective psychosocial psychostimulant recruit relapse patients response safety and feasibility safety assessment sham-controlled study success therapy development timeline treatment response visual stimulus

Abstinence Admission activity Affect Aftercare Alcohols American Anhedonia Animal Model Animals Anterior Area Back Behavioral Paradigm Bilateral Bioethics Consultants Biological Biological Markers Biometry Blinded Brain Case Study Cessation of life Chronic Clinic Clinical Clinical Data Clinical Trials Controlled Study Cross-Over Studies Crossover Design Cues Deep Brain Stimulation Drug Metabolic Detoxication Drug Screening Drug usage Electrophysiology (science)Enrollment Equilibrium Event Experimental Designs FDA approved Feasibility Studies Functional Magnetic Resonance Imaging Functional disorder Glutamates Human Implant Impulsivity Incidental Findings Individual Inpatients Intervention Knowledge Life Measurement Measures Medial Methamphetamine Methamphetamine use disorder Monitor Morbidity - disease rate Movement Disorders Neurology Neurons Neurosciences Neurosurgeon Nucleus Accumbens Obsessive-Compulsive Disorder Operative Surgical Procedures Opioid Outcome Patient Self-Report Persons Pharmaceutical Preparations Pharmacotherapy Phase Phenotype Physiologic pulse Placebos Play Prefrontal Cortex Procedures Psychiatrist Publishing Randomized Recording of previous events Refractory Reporting Rest Rewards Risk Taking Role Safety Signal Transduction Stimulant Stimulus Stream Structure Substance Use Disorder Synapses Technology Testing Time Treatment outcome United States Substance Abuse and Mental Health Services Administration Urine Ventral Tegmental Area addiction arm clinical outcome assessment cognitive process craving design evidence base experience improved methamphetamine use mortality neural neural circuit novel novel strategies phase 2 study preventable death prospective psychosocial psychostimulant recruit relapse patients response safety and feasibility safety assessment sham-controlled study success therapy development timeline treatment response visual stimulus

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项目摘要

Abstract: Substance use disorders are prevalent, cause significant morbidity, and are a common cause of preventable death. In contrast to alcohol and opioids, there are currently no FDA approved pharmacotherapies for methamphetamine use disorder (MUD), despite extensive efforts at prior medication trials. Psychosocial interventions are used to treat MUD, but many individuals remain refractory, highlighting the continued need for novel treatment development. Our understanding of the neural basis of addiction has grown in recent decades, underscoring the potential to selectively target addiction-related brain areas such as the nucleus accumbens (NAc). Deep brain stimulation is commonly used to treat movement disorders, as well as obsessive compulsive disorder, and allows chronic stimulation of subcortical brain structures, such as NAc. A growing body of animal model and human clinical data suggests NAc stimulation may be beneficial in the treatment of addiction. Here we propose a two-phase study, to test DBS of bilateral NAc for the treatment of MUD. Under the UG3 phase, we will enroll a small number of subjects (n=5) with treatment-refractory MUD and will employ a subject- and rater-blinded cross-over design using subjects as their own control. Subjects will receive inpatient detoxification, followed by DBS surgery, then 1 month of residential substance use disorder treatment, and 12 weeks of psychosocial interventions, along with 18 months of monitored DBS programming (subjects randomized to 6- months-sham then 12-months-active stimulation vs. active-then-sham treatment). Our clinical outcomes are methamphetamine use as measured by timeline followback and confirmed by urine drug screens, and self- reported methamphetamine craving. We will also carefully assess safety and feasibility of the study procedures. To investigate circuit-based target engagement, we will test for changes in activity during cue-craving and at rest with longitudinal functional MRI (fMRI) and local field potential recording (pre-DBS programming, 6-, 12-, and 18-months post-surgery). The Medtronic Percept implantable pulse generator allows recording from the implanted DBS leads, providing local field potential recording from the NAc itself during craving events experienced in daily life and with cue-craving presentation in the clinic. If our pre-hoc safety, feasibility and clinical and target engagement endpoints are achieved, we will proceed to the UH3 phase. In this phase, we will conduct a randomized, subject- and rater-blinded, sham-controlled trial of DBS for methamphetamine use disorder (n=20). Our design will be informed by UG3 findings (e.g., to determine expected time course for DBS response) and will seek to test whether NAc DBS added to standard psychosocial interventions provides clinical improvement in reducing methamphetamine use and craving above and beyond sham intervention. We will further explore the underlying mechanisms associated with DBS treatment response by investigating circuit- based fMRI signal and electrophysiological recordings of NAc. Through our experimental design, we have strived for the optimal balance between maintaining safety while deriving maximal information about human MUD.

抽象的：药物使用障碍很普遍，引起明显的发病率，是可预防的常见原因死亡。与酒精和阿片类药物相反，目前尚无FDA批准的药物治疗尽管在先前的药物试验中进行了广泛的努力，但甲基苯丙胺的使用障碍（MUD）。社会心理干预措施用于治疗泥浆，但许多人仍然难治性，强调了持续的需求新的治疗发展。我们对成瘾的神经基础的理解在近几十年来增强了，强调有选择性靶向与成瘾相关的大脑区域（例如伏隔核）的潜力（NAC）。深脑刺激通常用于治疗运动障碍以及强迫性强迫疾病，并允许慢性刺激皮质下脑结构，例如NAC。越来越多动物的身体模型和人类临床数据表明，NAC刺激可能对成瘾的治疗有益。这里我们提出了一项两阶段的研究，以测试双侧NAC的DBS用于治疗泥浆。在UG3阶段，我们将使用少数受试者（n = 5）和治疗 - 饮食泥浆，并将采用受试者和受试者 - 用主题作为自己的控制，将跨界设计的跨界设计。受试者将接受住院排毒，然后进行DBS手术，然后进行1个月的住宅药物使用障碍治疗，12周社会心理干预措施，以及18个月的监测DBS编程（受试者随机分别为6-- 几个月，然后12个月活跃的刺激与主动刺激）。我们的临床结果是按时间轴后卫测量的甲基苯丙胺使用，并由尿液药物筛查确认，自我据报道甲基苯丙胺的渴望。我们还将仔细评估研究程序的安全性和可行性。为了调查基于电路的目标参与，我们将测试提示和休息期间活动的变化具有纵向功能MRI（fMRI）和局部现场潜在记录（PER-DBS编程，6-，12-和手术后18个月）。 Medtronic感知植入脉冲发生器允许从植入的DBS线索，在渴望事件中提供NAC本身的本地现场潜在记录在日常生活中经验丰富，并在诊所中享受提示的表现。如果我们的事前安全，可行性和实现了临床和目标参与终点，我们将进入UH3阶段。在这个阶段，我们将进行甲基苯丙胺的随机，受试者和评估的DBS的假手术对照试验障碍（n = 20）。 UG3调查结果将告知我们的设计（例如，确定DBS的预期时间课程响应）并将寻求测试NAC DB是否添加到标准的心理社会干预措施中提供临床改善甲基苯丙胺的使用和渴望超越假干预。我们将进一步探索与DBS治疗反应相关的潜在机制，通过研究电路 - 基于NAC的fMRI信号和电生理记录。通过我们的实验设计，我们努力为了保持安全性，同时获得有关人类泥浆的最大信息之间的最佳平衡。