Addiction Treatment in Russia:Oral and Depot Naltrexone

描述(由申请人提供)：在俄罗斯，海洛因成瘾的通常治疗包括戒毒和2-4周的康复，并转介到门诊随访。虽然大多数患者都完成了住院治疗，但很少有患者坚持随访，复发率很高。需要更有效的治疗方法，特别是考虑到海洛因成瘾的流行已导致艾滋病毒和其他传染病的传播。最近完成的一项针对52名患者的随机研究显示，口服纳曲酮(ON)或口服纳曲酮安慰剂(ONP)在预防复发和降低艾滋病毒风险方面有效，但辍学是一个问题，只有44%的ON患者被证明在6个月内没有复发，而ONP患者的这一比例为16%。一项对280名患者进行的更大规模的研究将进一步评估这些早期结果，并确定加入SSRI是否会改善结果。这项研究的招募工作已接近完成，但尚未完成，尚未获得结果数据。 我们认为仓库注射纳曲酮(DIN)也可以改善保留率和疗效，在这项研究中，我们建议将其与DIN进行比较。DIN未被批准在俄罗斯使用，我们希望这项研究的结果能被俄罗斯当局接受，并可能批准其广泛使用。因此，我们建议采用安慰剂对照、双盲/双模拟设计，因为俄罗斯的FDA要求将安慰剂对照试验作为批准药物治疗的条件。参与者将是在圣彼得堡戒毒医院戒毒的男性和女性海洛因成瘾者，他们的家人愿意并有能力监督服药依从性并促进后续行动。在给予知情同意并确认没有生理依赖后，300名患者将被随机分配到三个组中，每组100人，进行为期6个月的治疗：口服纳曲酮(ON)+可注射纳曲酮安慰剂(DINP)；口服纳曲酮安慰剂(ONP)+可注射纳曲酮(DIN)；或ONP+DINP。所有患者将接受每两周一次的临床管理/依从性增强咨询。评估将在基线、药物治疗6个月期间的每两周一次的预约以及药物治疗结束后的3个月和6个月进行。主要结果将是1-6个月的无复发比例；次要结果将是辍学时间、阿片类药物阳性尿液、艾滋病毒风险、酒精和其他药物的使用、精神症状和其他总体调整措施。我们假设，服用DIN的结果将比服用On更好，而且每种药物都比安慰剂更有效。

DESCRIPTION (provided by applicant): The usual treatment of heroin addiction in Russia involves detoxification and 2-4 weeks of rehabilitation with referral to outpatient follow-up. Though most patients complete inpatient treatment, few keep follow-up appointments and relapse rates are high. More effective therapies are needed, especially in view of the epidemic of heroin addiction that has resulted in the spread of HIV and other infectious diseases. A recently completed study of 52 patients randomized to oral naltrexone (ON) or oral naltrexone placebo (ONP) has shown efficacy in preventing relapse and reducing HIV risk but dropout was a problem with only 44% of ON patients proven to have not relapsed by 6 months as compared to 16% of ONP patients. A larger study of 280 patients randomized to ON or ONP with or without fluoxetine will further evaluate these early results and determine if adding a SSRI improves outcome. Recruitment into this study is almost completed but is not finished and outcome data are not yet available. We think that retention and outcome can be also improved by depot injectable naltrexone (DIN), and in this study we propose to compare ON with DIN. DIN is not approved for use in Russia and we would like the results of this study to be acceptable to Russian authorities that might approve it for general use. Thus we propose a placebo-controlled, double-blind/double-dummy design since a placebo-controlled trial is required by the Russian equivalent of our FDA as a condition for approval of a pharmacotherapy. Participants will be male and female heroin addicts who have been detoxified in addiction treatment hospitals in St. Petersburg and have a family member willing and able to supervise medication compliance and facilitate follow-up. After giving informed consent and confirming the absence of physiologic dependence, 300 patients will be randomly assigned to a 6-month treatment in one of three groups of 100 each: oral naltrexone (ON) + depot injectable naltrexone placebo (DINP); oral naltrexone placebo (ONP) + depot injectable naltrexone (DIN); or ONP + DINP. All patients will receive biweekly clinical management/compliance enhancement counseling. Assessments will be done at baseline, at each biweekly appointment during the 6-month of medication treatment, and at 3 and 6 months following the end of the medication. Primary outcome will be the relapse free proportion at months 1-6; secondary outcomes will be time to dropout, opioid positive urines, HIV risk, use of alcohol and other drugs, psychiatric symptoms, and other measures of overall adjustment. We hypothesize that outcomes will be better with DIN than ON, and that each will be more effective than placebo.