Laboratories for Early Clinical Evaluation of Pharmacotherapies for Substance Use Disorders

物质使用障碍药物治疗早期临床评价实验室

基本信息

批准号：
10553087
负责人：
ALBERT JOSEPH ARIAS
金额：
$ 64.71万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10553087
关键词：
Adverse event Agonist Alcohols Amygdaloid structure Anti-Anxiety Agents Anticonvulsants Anxiety Behavioral Benefits and Risks Brain Brain imaging Buprenorphine Clinical Clinical Research Cocaine Cocaine use disorder Collaborations Cues Data Development Development Plans Dose Double-Blind Method Dropout Drug Interactions Emotional Face Frequencies Functional Magnetic Resonance Imaging Funding Future Grant Hippocampus Hour Human Hypothalamic structure Impulsivity Inpatients Institutional Review Boards Laboratories Magnetic Resonance Imaging Measures Medical Naloxone National Institute of Drug Abuse Opioid Outpatients Participant Patients Pharmaceutical Preparations Pharmacotherapy Phase Phase II Clinical Trials Phenotype Placebos Plasma Pre-Clinical Model Pulse Oximetry Randomized Research Research Design Resources Rodent Safety Sample Size Sampling Studies Scanning Self Administration Serious Adverse Event Serotonin Receptor 5-HT2C Signal Transduction Spectrum Analysis Stress Suboxone Substance Use Disorder Technology Therapeutic Treatment Protocols Universities Virginia Visual Withdrawal Withdrawal Symptom abuse liability analog anxiety symptoms clinical development cocaine cue comorbidity craving cue reactivity drug craving early phase clinical trial experimental study functional MRI scan gamma-Aminobutyric Acid imaging study improved infrastructure development neural circuit neuroimaging novel opioid use disorder opioid withdrawal placebo controlled study pre-clinical research clinical testing response safety assessment safety study side effect stress reactivity

项目摘要

Funded for the last 4 years by a medication development center grant (U54DA038999), our research group at the Institute for Drug and Alcohol Studies (IDAS) at Virginia Commonwealth University has established the expertise and resources to execute early clinical trials of potential pharmacotherapies for substance use disorders including opioid and cocaine use disorders as well as comorbid opioid+cocaine use disorder. Under that funding, medication development studies were carried out using preclinical models, phase I inpatient studies, brain imaging studies, and behavioral laboratory phenotyping studies for novel compounds for opioid and cocaine use disorders. One of the novel compounds we have examined for opioid, cocaine, and comorbid opioid+cocaine use disorders is the 5-HT2CR agonist lorcaserin. This research was based on our preclinical data that lorcaserin significantly reduces opioid self-administration and opioid and cocaine cue elicited responding in rodents8. In response to RFA-DA-19-018, we propose to maintain and enhance the established medication development infrastructure at IDAS to support Phase I and Phase 2 clinical trials in collaboration with the Division of Therapeutics and Medical Consequences at NIDA. As a demonstration project of the ability of IDAS to conduct early phase clinical trials, we propose to assess safety, target engagement, and preliminary measures of efficacy, for lorcaserin in combination with buprenorphine for opioid use disorder. Specific Aims for Demonstration Project: Experiment 1 (0-18 months). Aim 1: Examine side effects and drug interactions between lorcaserin and buprenorphine-naloxone in participants with opioid use disorder who are in MAT with buprenorphine-naloxone. Aim 2: Examine effects of lorcaserin on subjective measures of drug craving compared to placebo in participants with opioid use disorder who are in MAT with buprenorphine-naloxone. Experiment 2 (Post Experiment I if approved by NIDA). Aim 1: Examine effect of lorcaserin on opioid cue related brain directional (effective) connectivity compared to placebo in participants with opioid use disorder who are in MAT with buprenorphine-naloxone. Aim 2: Examine effect of lorcaserin on impulsivity related effective connectivity compared to placebo in participants with opioid use disorder who are in MAT with buprenorphine-naloxone. Exploratory Aim: Examine noninvasively, using MRI spectroscopy, the effects of lorcaserin compared to placebo on brain GABA concentrations in opioid use disorder participants who are in MAT with buprenorphine- naloxone.

我们的研究小组由药物开发中心赠款（U54DA038999）资助了过去4年弗吉尼亚联邦大学的毒品和酒精研究研究所（IDA）已建立专业知识和资源，以进行潜在药物使用药物的早期临床试验包括阿片类药物和可卡因的疾病以及合并症的阿片类药物+可卡因使用障碍。在下面使用临床前模型进行了资金，药物开发研究阿片类药物的新化合物研究，大脑成像研究和行为实验室表型研究和可卡因使用障碍。我们检查了阿片类药物，可卡因和合并症的一种新颖化合物之一阿片类药物+可卡因的使用障碍是5-HT2CR激动剂Lorcaserin。这项研究基于我们的临床前 Lorcaserin显着降低了阿片类药物自我给药的数据以及阿片类药物和可卡因提示引起在啮齿动物中响应8。为了响应RFA-DA-19-018，我们建议维护和增强在IDAS建立了药物开发基础设施，以支持I阶段和第二阶段临床与NIDA的治疗和医学后果的合作试验。作为 IDA进行早期临床试验的能力的演示项目，我们建议评估安全性，劳卡森与丁丙诺啡结合的目标参与和疗效的初步措施阿片类药物使用障碍。示范项目的具体目标：实验1（0-18个月）。 AIM 1：检查劳卡森和丁丙诺啡诺在中的副作用和药物相互作用患有阿片类药物使用障碍的参与者与丁丙诺啡合酮息息相关。 AIM 2：与安慰剂相比，检查Lorcaserin对药物渴望的主观测量的影响患有阿片类药物使用障碍的参与者与丁丙诺啡合酮息息相关。实验2（实验后，如果获得NIDA批准）。 AIM 1：与相比在患有丁丙诺啡 - 诺氧酮垫中的阿片类药物使用障碍参与者中的安慰剂。 AIM 2：与安慰剂相比，检查Lorcaserin对冲动性相关的有效连通性的影响患有阿片类药物使用障碍的参与者与丁丙诺啡合酮息息相关。探索性目的：使用MRI光谱法检查，劳卡瑟蛋白的作用与安慰剂在阿片类药物使用障碍参与者中的脑GABA浓度上与丁丙诺啡一起纳洛酮。