BUPRENORPHINE MAINT FOR COCAINE ABUSING OPIOID ADDICTS

这是一个竞争性的更新，要求三年的资金，24周 双盲、双模拟随机对照临床试验， 低剂量丁丙诺啡（4 mg SL）维持治疗的临床疗效 每日）、高剂量丁丙诺啡（每日12 mg SL）或美沙酮（65 mg PO 每日）的可卡因滥用阿片依赖患者（n = 120）。 我们有 假设维持丁丙诺啡，一种部分阿片类拮抗剂， 具有有限的激动剂活性，不会通过 改善焦虑或增强可卡因欣快症，因此将具有 与美沙酮维持治疗相比，改善了疗效。 在第一 在最初两年的资助期内，我们完成了一项为期16个月的 剂量范围探索研究，以确定降低 阿片类药物和可卡因滥用，修改了双盲研究方案 研究并开始入组双盲研究。 修改 双盲试验包括：1）高、低剂量比较 丁丙诺啡和大剂量美沙酮; 2）街头成瘾者的登记， 确保维持双盲; 3）严格的资格 确保药物使用严重程度均匀性的要求， 基于抑郁症的存在/不存在的随机化前分层; 4)在整个研究期间使用意外事件，以确保 治疗组间具有临床意义的结局差异， 研究与标准治疗方案的相关性; 5）延长治疗时间 临床试验至24周，以提供足够的治疗时间 研究对街头吸毒者的有效性，并促进汇集研究结果 我们最近完成了两种剂量的丁丙诺啡（2 mg， 6 mg）和美沙酮（35 mg，65 mg）; 6）将样本量增加至120 受试者增加统计功效，以评价 改善和患者治疗匹配。 评价替代 维持剂，如丁丙诺啡，具有潜在的改善， 与美沙酮相比， 阿片类药物的使用是必不可少的，因为美沙酮中的可卡因滥用保持不变 患者是地方性的，并破坏了这种治疗的有效性。

This is a competing renewal requesting three years funding for a 24 week double blind, double dummy randomized controlled clinical trial comparing the clinical efficacy of maintenance on low dose buprenorphine (4 mg SL daily), high dose buprenorphine (12 mg SL daily) or methadone (65 mg PO daily) for cocaine abusing opiate dependent patients (n = 120). We have hypothesized that maintenance on buprenorphine, a partial opioid antagonist with limited agonist activity, will not reinforce cocaine use by ameliorating dysphoria or enhancing cocaine euphoria and thus will have improved efficacy compared to maintenance on methadone. During the first 16 months of the initial two year funding period, we completed a dose-ranging study to determine optimal buprenorphine dose(s) to reduce opioid and cocaine abuse, modified the study protocol for the double blind study and initiated enrollment in the double blind study. Modifications in the double blind study include: 1) comparison of high and low dose buprenorphine and high dose methadone; 2) enrollment of street addicts to ensure maintenance of the double blind; 3) stringent eligibility requirements to ensure homogeneity of drug use severity and pre-randomization stratification based on presence/absence of depression; 4) use of contingencies throughout study to ensure maximal likelihood of clinically significant outcome differences among treatment groups and relevance of study to standard treatment programs; 5) increased length of clinical trial to 24 weeks to provide sufficient time for treatment effectiveness in street addicts and to facilitate pooling the study results with our recently completed comparison of two doses of buprenorphine (2 mg, 6 mg) and methadone (35 mg, 65 mg); 6) increased sample size to 120 subjects to increase statistical power to evaluate predictors of improvement and patient-treatment matching. Evaluation of alternative maintenance agents, such as buprenorphine, with potentially improved efficacy compared to methadone for the reduction of cocaine and illicit opioid use is essential since cocaine abuse among methadone maintained patients is endemic and undermines the effectiveness of this treatment.