Pharmacotherapy for Cocaine Dependence: d-cycloserine with Contingency Management

描述(申请人提供)：可卡因依赖是一个发病率很高的公共卫生问题，然而FDA还没有批准有效的可卡因依赖药物治疗方法。与以前的药物研究不同，这项探索性临床试验将测试d-环丝氨酸(Dcs)对改善可卡因依赖的基于学习的行为治疗的能力。DCs是一种NMDA部分激动剂，已被证明在临床前模型中显著改善学习，包括消除可卡因条件性位置偏爱和阻断可卡因再获得，并改进基于消退学习的暴露疗法治疗多发性焦虑症。这项第二阶段临床试验将研究结合应急管理(CM)和新颖的家庭环境暴露疗法治疗可卡因依赖的行为治疗的药理学(DC)增强。将使用高幅度的CM激励措施来促进在以家庭为基础的暴露会话中戒除必要的可卡因。参与者将被随机分成两组：1.服用安慰剂(CM+PL)的CM组，以及2.服用DC(CM+DC)的CM组。在小组分配后的19天内，参与者将每周三次(周一、周三、周五)到实验室报到，提供尿样，领取应急代金券，并完成药物使用、渴求、情绪、戒断和戒断自我效能的评估。在周一和周五的研究访问期间(在实验室访问结束后，回到家庭环境中进行暴露治疗之前)，将使用dcs(50毫克)或安慰剂。随访将在CM完成后1周、1个月和3个月进行，在此期间将获得药物使用(自我报告和尿检)、渴求、情绪和戒断的测量。两组间CM术后持续戒断的比较将是主要的结果衡量标准。在最初的实验室会话中，一系列学习/认知任务将测试可能有助于治疗效果的DC增强的学习/认知形式。该项目将测试一种新的可卡因依赖干预措施的有效性，该干预措施基于已知有效的可卡因依赖治疗(CM)、消退学习理论的原理，以及一种被证明总体上可以改善临床前学习的药物，包括戒除可卡因条件作用，以及基于临床学习的焦虑症暴露治疗。这项研究可能表明，在消除意外情况后，增加具有成本效益的措施(家庭暴露会议和分布式控制系统)，以扩大CM的惠益，因此可能会增加CM在社区环境中的传播。 公共卫生相关性：FDA尚未批准用于治疗可卡因依赖的药物。这项拟议的研究将测试一种新的可卡因药物开发方法，这种方法与其他可卡因药物开发尝试不同，其他可卡因药物开发尝试试图从药理上改变可卡因的效果。这项研究将测试d-环丝氨酸(Dcs)改善焦虑症行为治疗的能力，以改善可卡因依赖的行为治疗。这项试验最终可能转化为可卡因依赖医疗治疗的重大进步。

DESCRIPTION (provided by applicant): Cocaine dependence is a public health problem with substantial morbidity, however no effective pharmacotherapy for cocaine dependence has been approved by the FDA. Unlike previous medication studies that have sought to pharmacologically reduce cocaine reinforcement, seeking or craving, this exploratory clinical trial will test d-cycloserine (DCS) for its ability to improve learning-based behavioral treatment of cocaine dependence. DCS is an NMDA partial agonist that has been shown to robustly improve learning in preclinical models, including extinction of cocaine conditioned place preference and blockade of cocaine reacquisition, and to improve extinction-learning based exposure therapy for multiple anxiety disorders. This Phase II clinical trial will investigate the pharmacological (DCS) enhancement of a behavioral treatment combining contingency management (CM) and novel home-environment exposure therapy sessions for cocaine dependence. High magnitude CM incentives will be used to promote the cocaine abstinence necessary for extinction in home-based exposure sessions. Participants will be randomized into 2 groups: 1. CM with placebo (CM+PL), and 2. CM with DCS (CM+DCS). For 19 days after group assignment, participants will report to the laboratory 3 times per week (Mon, Wed, Fri) to provide urine samples, receive contingent vouchers, and complete assessments of drug use, craving, mood, withdrawal, and quit self-efficacy. DCS (50 mg) or placebo will be administered on Mon and Fri study visits (at the end of the lab visit before returning to the home environment for exposure sessions during the time of DCS action). Follow-up visits will be conducted at 1 week, 1 month, and 3 months post-CM completion, during which time measures of drug use (self-reported and urinalysis), craving, mood, and withdrawal will be obtained. Comparison of continuous abstinence post-CM between the groups will be the primary outcome measure. During an initial laboratory session, a battery of learning/cognitive tasks will test for forms of learning/cognition enhanced by DCS that might contribute to the treatment effect. This project will test the efficacy of a novel intervention for cocaine dependence that was developed based on a known efficacious cocaine dependence treatment (CM), principles of extinction learning theory, and a medication shown to improve preclinical learning in general, including extinction of cocaine conditioning, and clinical learning-based exposure treatment of anxiety disorders. The study may indicate cost effective additions (home exposure sessions and DCS) to extend CM benefit after the removal of contingencies, and therefore may increase the dissemination of CM in community settings. PUBLIC HEALTH RELEVANCE: No medication has been approved by the FDA for the treatment of cocaine dependence. The proposed study will test a novel approach to cocaine medications development that differs from other attempts at cocaine medications development, which have sought to pharmacologically alter the effects of cocaine. This study will test the ability of d-cycloserine (DCS), which has improved behavioral treatment of anxiety disorders, to improve behavioral treatment of cocaine dependence. This trial may ultimately translate into significant advancement in the medical treatment of cocaine dependence.