DISULFIRAM FOR COCAINE ABUSE IN BUPRENORPHINE TREATMENT

双硫仑治疗丁丙诺啡治疗中可卡因滥用

• 批准号: 6362852
• 负责人: Richard S Schottenfeld
• 金额: $ 42.74万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-10 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6362852
• 关键词: buprenorphine; clinical research; clinical trials; cocaine; disulfiram; dopamine beta monooxygenase; drug abuse chemotherapy; drug screening /evaluation; human subject; human therapy evaluation; opiate alkaloid; placebos

DESCRIPTION: Applicant's Abstract We are proposing a placebo-controlled clinical trial to evaluate the efficacy and potential mechanisms of action of disulfiram (vs. placebo) for treating cocaine abuse in buprenorphine maintained subjects (N=180) with concurrent opiate dependence and cocaine abuse or dependence. Because of its safety in overdose situations and decreased abuse liability, buprenorphine may be widely used outside of narcotic treatment programs (e.g., in primary care or office settings). Thus it is of considerable importance to evaluate adjunctive pharmacologic treatments that may improve its efficacy for treating concurrent opioid and cocaine dependence. Convergent findings from epidemiologic, laboratory and clinical trials, including the results of a preliminary study conducted in preparation for this application, support the potential efficacy of disulfiram; a medication used to treat alcohol dependence, for the treatment of cocaine abuse. Disulfiram's efficacy for cocaine may result from preventing concurrent alcohol use, which can precipitate cocaine relapse, or from its inhibition of dopamine-beta-hydroxylase, the enzyme that converts dopamine to norepinephrine, which may reduce craving and increase the anxiogenic or dysphoric effects of cocaine administration. Accordingly, to explore whether disulfiram efficacy for cocaine dependence is mediated by its effects on alcohol consumption or on central DBH and dopamine activity, baseline alcohol severity, and DBH genotypes which are associated with high or low DBH activity will be evaluated as predictors of differential treatment response. Subjects meeting DSM-IV criteria for opioid dependence and cocaine abuse or dependence will be stabilized on buprenorphine (24 mg daily, sublingual tablets) for 2 weeks before being randomly assigned to 12 weeks of treatment with disulfiram 250 mg daily or placebo, provided under double-blind conditions. An urn randomization procedure will be used to balance the treatment groups on gender, depressive symptoms, baseline alcohol use and cocaine use severity. Manual-guided group drug counseling will be the platform psychotherapy provided weekly for all subjects. Primary outcome measures include reductions in cocaine use assessed by three times weekly urines and self-report. Secondary outcomes measures include reductions in illicit opioid use and HIV risk behaviors. Primary data analyses will focus on an intention-to-treat sample and will utilize mixed models analysis of variance and a factorial analysis of variance. The effects of baseline predictors and their interactions with treatment condition on these outcomes will also be evaluated.

描述：申请人的摘要 我们正在提议进行一项安慰剂对照临床试验来评估疗效 以及双硫仑（与安慰剂）治疗的潜在作用机制 丁丙诺啡维持受试者中可卡因滥用 (N=180) 阿片依赖和可卡因滥用或依赖。由于其安全性 过量情况和减少滥用倾向，丁丙诺啡可能被广泛使用 在麻醉治疗计划之外使用（例如，在初级保健或办公室 设置）。因此，评估辅助手段就显得尤为重要。 可能会提高其治疗并发的疗效的药物治疗 阿片类药物和可卡因依赖。流行病学的综合发现， 实验室和临床试验，包括初步研究的结果 为该应用做准备而进行的，支持潜在功效 双硫仑；用于治疗酒精依赖的药物，用于治疗 可卡因滥用。双硫仑对可卡因的功效可能来自于预防 同时饮酒，可能会导致可卡因复发，或从其 抑制多巴胺-β-羟化酶，该酶将多巴胺转化为 去甲肾上腺素，可能会减少渴望并增加焦虑或 可卡因给药的烦躁效应。据此，探讨是否 双硫仑治疗可卡因依赖的功效是通过其对 饮酒量或中枢 DBH 和多巴胺活动、基线酒精 严重程度以及与高或低 DBH 活性相关的 DBH 基因型 将被评估为差异治疗反应的预测因子。科目 符合 DSM-IV 关于阿片类药物依赖和可卡因滥用或依赖的标准 将用丁丙诺啡（每日 24 毫克，舌下含片）稳定 2 次 随机分配接受 12 周双硫仑治疗前几周 每日 250 毫克或安慰剂，在双盲条件下提供。一个瓮 将使用随机化程序来平衡治疗组的性别， 抑郁症状、基线饮酒和可卡因使用严重程度。 人工指导的团体药物咨询将成为心理治疗提供的平台 所有科目每周一次。主要结果指标包括减少可卡因 通过每周三次尿液和自我报告评估使用情况。次要结果 措施包括减少非法阿片类药物的使用和艾滋病毒危险行为。 主要数据分析将侧重于意向治疗样本，并将 利用混合模型方差分析和因子方差分析。 基线预测因素的影响及其与治疗的相互作用 还将评估这些结果的条件。