BUPRENORPHINE MAINT FOR COCAINE ABUSING OPIOID ADDICTS

这是一项相互竞争的续订，申请为期三年的24周资金 双盲、双模拟随机对照临床试验 小剂量丁丙诺啡(4mgSL)维持治疗的临床疗效 每日)、大剂量丁丙诺啡(每天12毫克SL)或美沙酮(65毫克PO 每日)用于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，不会加强可卡因的使用 改善烦躁不安或增强可卡因欣快感，因此将有 与美沙酮的维持治疗相比，疗效有所改善。在第一次 在最初的两年资助期中的16个月，我们完成了 丁丙诺啡最佳减量剂量的量程研究(S) 阿片类药物和可卡因滥用，修改了双盲研究方案 学习，并开始招收双盲学习。中的修改 双盲研究包括：1)高、低剂量比较 丁丙诺啡和大剂量美沙酮；2)街头吸毒者登记参加 确保双盲的维护；3)严格的资格 确保药物使用严重程度和 根据抑郁症的存在/不存在进行预随机化分层； 4)在整个研究过程中使用应急措施，以确保最大可能性 治疗组和对照组之间的临床显著结果差异 研究与标准治疗方案的相关性；5)增加 临床试验延长至24周，为治疗提供充足的时间 对街头吸毒者的有效性，并便于汇集研究结果 我们最近完成了两种剂量丁丙诺啡(2毫克， 6)将样本量增加到120 受试者将增加评估预测因素的统计能力 改善和医患匹配。对备选方案的评估 维持剂，如丁丙诺啡，可能会得到改善 与美沙酮在减少可卡因和非法毒品方面的疗效比较 阿片类药物的使用是必要的，因为美沙酮中的可卡因滥用仍然存在 患者是地方病，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.