Pharmacotherapy for Cocaine Dependence

描述(申请人提供)：可卡因依赖有各种不良后果，并已被证明难以治疗。包括社区强化模式和认知行为疗法/复发预防在内的行为干预已被证明是有效的。可能起到有效辅助作用的药物一直难以捉摸。最近的灵长类自我给药数据(Negus，2002)，最近的几份报告，以及最近一项大型临床试验的完成/分析支持了对激动剂/替代方法的进一步研究。尽管如此，靶向药物、剂量和持续时间必须进一步评估。 本申请提出了一项大范围(140个S，35个/组)、长疗程(6个月)的严格随机盲法临床试验。将在不同剂量范围内检查d-苯丙胺的缓释情况。对于PBO，在相同的胶囊中给予45毫克、60毫克或80毫克。将使用核黄素、尿液筛查和MEMS配药瓶采取严格的合规措施。同意后将有10天的时间，在此期间必须提供BZ阳性尿液筛查，并在此期间进行摄取和评估。服药10天后，将进行20周的稳定服药。接下来是减药期和四周的行为治疗，治疗后的随访将在1个月和3个月。摄入量评估将包括标准化措施(例如，ASI、SCID、Ham A/D、渴求问卷；HIV、EKG、TB、尿检)。每周将重复进行三次尿检。EKG将每两周进行一次。手动认知行为疗法将每周一次。在准备阶段、维持阶段、剂量减少阶段和最后三个非药物周，将定期采集血液样本。这一设计结合了主要特征和细节，符合NIDA关于激动剂评估最佳策略的共识审查(2002年1月)。

DESCRIPTION (provided by applicant): Cocaine dependence has diverse adverse consequences and has proven difficult to treat. Behavioral interventions, including Community Reinforcement Model and Cognitive Behavior Therapy/Relapse Prevention have proven effective. Medications that might serve as effective adjuncts have been elusive. Recent primate self-administration data (Negus, 2002), several recent reports, and completion/analysis of a recent large clinical trial support further study of the agonist/ replacement approach. Still, target medications, dose, and duration must be further evaluated. This application proposes a large (140 S's, 35/group), long duration (6 month) rigorous blind randomized clinical trial. Sustained release d-amphetamine will be examined across dose range. of PBO, 45 mg, 60 mg, or 80 mg administered in identical capsules. Rigorous compliance measures using riboflavin, urine screens, and MEMS dispensing bottles will be applied. Consent will be followed by a 10 day period in which BZ positive urine screens must be provided and during which Intake and Evaluation will proceed. Medication run-up of 10 days will be followed by 20 weeks of stable medication. A dose reduction period and four weeks of behavior therapy alone will follow, Post treatment follow-up will be at 1 and 3 months. Intake evaluation will include standardized measures (.e.g. ASI, SCID, HAM A/D, Craving Questionnaire; HIV, EKG, TB, urine screens). There will be repeated weekly measures with thrice weekly urine screens. EKGs will be bi-weekly. Manual Driven Cognitive Behavior Therapy will be weekly. Blood samples will be obtained at regular intervals during run-up, maintenance, dose reduction and in the final three non-medication weeks. This design incorporates both major features and details in accord with NIDA's consensus review (January 2002) on optimal strategies for agonist evaluation.