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: 6039806
• 负责人: Richard S Schottenfeld
• 金额: $ 37.95万
• 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/6039806
• 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：申请者摘要 我们建议进行一项安慰剂对照的临床试验来评估疗效。 以及双硫仑(与安慰剂相比)治疗的潜在作用机制 丁丙诺啡维持者(N=180)并发可卡因滥用 鸦片依赖和可卡因滥用或依赖。因为它是安全的 过量用药和减少滥用倾向，丁丙诺啡可能会广泛应用 在麻醉药品治疗方案之外使用(例如，在初级保健或办公室 设置)。因此，对修饰语的评价就显得尤为重要 可能提高其治疗并发疾病疗效的药物治疗 阿片类药物和可卡因依赖。来自流行病学的一致发现， 实验室和临床试验，包括初步研究的结果 为此应用程序进行准备，支持潜在疗效 用于治疗酒精依赖的药物；用于治疗的 可卡因滥用。双硫兰对可卡因的疗效可能源于预防 同时饮酒，这可能会导致可卡因复发，或者是因为 抑制多巴胺-β-羟基酶，该酶将多巴胺转化为 去甲肾上腺素，可以减少饥饿感，增加引起焦虑的或 可卡因给药后的烦躁不安。因此，要探索是否 双硫仑对可卡因依赖的疗效是通过其对 酒精摄入量或对中枢胸径和多巴胺活性的影响，基线酒精 严重程度和与胸径活动高或低相关的胸径基因型 将被评估为区别治疗反应的预测因子。科目 符合DSM-IV阿片依赖和可卡因滥用或依赖标准 将稳定在丁丙诺啡(每天24毫克，舌下片)上，共2次 在随机分配给双硫仑治疗前12周 每日250毫克或安慰剂，在双盲条件下提供。骨灰盒 将使用随机化程序来平衡治疗组的性别， 抑郁症状、基线酒精使用和可卡因使用严重程度。 手动引导的团体药物咨询将为心理治疗提供平台 所有科目每周一次。主要结果衡量标准包括可卡因的减少 通过每周三次小便和自我报告来评估使用情况。次要结果 措施包括减少非法阿片类药物使用和艾滋病毒危险行为。 主要数据分析将重点放在意向治疗样本上，并将 利用混合模型的方差分析和因子分析的方差。 基线预测因子的作用及其与治疗的交互作用 还将对这些结果的条件进行评估。