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: 6634288
• 负责人: Richard S Schottenfeld
• 金额: $ 44.26万
• 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 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634288
• 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 我们正在提出一项安慰剂对照临床试验来评估功效 以及二硫兰氏鞭毛的作用机理（与安慰剂）治疗 丁丙诺啡中可卡因滥用受试者（n = 180）并发 鸦片依赖和可卡因滥用或依赖。因为它的安全 服药过量和滥用责任减少，丁丙诺啡可能广泛 在麻醉治疗计划之外使用（例如，在初级保健或办公室中 设置）。因此，评估辅助性非常重要 可以提高其并发治疗功效的药理治疗 阿片类药物和可卡因依赖性。来自流行病学的收敛发现， 实验室和临床试验，包括初步研究的结果 为了准备此应用而进行的，支持潜在功效 二硫仑用于治疗酒精依赖的药物 可卡因滥用。二硫仑对​​可卡因的功效可能是由于阻止 同时使用的酒精，可以沉淀可卡因复发或从其饮酒 抑制多巴胺β-羟化酶，将多巴胺转化为多巴胺的酶 去甲肾上腺素，可能会减少渴望并增加焦虑症或 可卡因给药的烦躁不安。因此，探索是否 可卡因依赖性的二硫仑疗法是由其对其影响的影响所介导的 饮酒或中央DBH和多巴胺活性，基线酒精 严重程度和与高或低DBH活性相关的DBH基因型 将评估为差异治疗反应的预测指标。主题 满足阿片类药物依赖和可卡因滥用或依赖的DSM-IV标准 将在丁丙诺啡（每天24毫克，舌下片剂）上稳定为2 在被随机分配到二硫酸治疗的12周之前几周 每天250毫克或安慰剂，在双盲条件下提供。一个 随机过程将用于平衡性别治疗组， 抑郁症状，基线饮酒和可卡因使用严重程度。 手动引导的小组药物咨询将是提供的平台心理治疗 所有主题每周一次。主要结果指标包括可卡因的减少 使用每周尿液和自我报告评估三次。次要结果 措施包括减少阿片类药物使用和HIV风险行为的减少。 主要数据分析将集中在意向性处理样本上，并将 利用差异的混合模型分析和方差分析。 基线预测因子及其与治疗的相互作用的影响 这些结果的条件也将得到评估。