DISULFIRAM FOR COCAINE ABUSE IN BUPRENORPHINE TREATMENT

描述：申请人摘要 我们建议进行一项安慰剂对照的临床试验， 和双硫仑（与安慰剂相比）用于治疗的潜在作用机制 丁丙诺啡维持受试者中的可卡因滥用（N=180）， 鸦片依赖和可卡因滥用或依赖。由于其安全性， 过量的情况和减少滥用的责任，丁丙诺啡可能广泛 在麻醉治疗方案之外使用（例如，在初级保健或办公室 设置）。因此，评价其可靠性是相当重要的 可能提高其治疗并发症的疗效的药物治疗 阿片类药物和可卡因依赖。来自流行病学， 实验室和临床试验，包括初步研究的结果 在本申请的准备过程中进行，支持潜在疗效 双硫仑;一种用于治疗酒精依赖的药物， 可卡因滥用。双硫仑对可卡因的疗效可能来自于预防 同时使用酒精，这可能会促使可卡因复发，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，这可能会减少渴望和增加焦虑或 可卡因给药的焦虑影响。因此，为了探索 双硫仑对可卡因依赖的疗效是通过其对 饮酒或中枢DBH和多巴胺活性，基线酒精 严重程度和与高或低胸径活性相关的胸径基因型 将作为不同治疗反应的预测因子进行评价。科目 符合DSM-IV阿片类药物依赖和可卡因滥用或依赖标准 将在丁丙诺啡（每日24 mg，舌下片剂）下稳定2 在随机分配至12周双硫仑治疗前10周 每日250 mg或安慰剂，在双盲条件下提供。一个骨灰盒 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。 手册指导的团体药物咨询将是提供的平台心理治疗 所有科目每周一次。主要结果指标包括可卡因的减少 通过每周三次排尿和自我报告评估使用情况。次要结局 这些措施包括减少非法阿片类药物使用和艾滋病毒风险行为。 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析因方差分析。 基线预测因素的影响及其与治疗的相互作用 对这些结果也将进行评估。

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.