Evaluation of Atomoxetine for Cocaine Dependence: A Pilot Trial

描述(由申请人提供)：本申请书是应DA-06-002号申请《物质相关疾病药物治疗的临床试验》的要求而写成的。可卡因滥用和依赖已被认为是一个重大的公共卫生问题，目前还没有广泛有效的药物可用。最近，使用激动剂替代或替代方法的研究，包括对d-苯丙胺和莫达非尼的研究，已经取得了令人振奋的结果。这一试点项目建议评估托莫西汀(Strattera)，这是一种目前在青少年和成人中用于治疗ADHD的化合物，用于治疗可卡因依赖。托莫西汀是一种去甲肾上腺素再摄取阻滞剂，它对多巴胺和5-羟色胺转运部位的亲和力相对较低。它已在临床实践中安全耐受，并与低滥用潜力有关。初步数据表明，其药效学效应与原型兴奋剂部分重叠，维持托莫西汀可以减少可卡因滥用志愿者对可卡因的主观反应和自我报告的可卡因欲望评级。这项申请建议进行一项单一、安慰剂对照、双盲、随机试点临床试验，以评估托莫西汀(Stattera)治疗可卡因依赖的疗效。正在寻求治疗药物滥用的可卡因依赖健康个人，将在仔细的医疗和精神筛查后登记，以确保他们在两周内适合进行这项研究。在随机分为两组(n=25/组)之前，患者将根据已知的影响可卡因滥用治疗结果的变量进行分层。在为期12周的试验中，患者将随机接受托莫西汀(每天80毫克，短暂引入)或与之匹配的安慰剂。所有患者都将参加每周一次的认知行为咨询会议。将采用应急管理程序，以增加出席人数和减少审判的自然减员。在整个试验过程中，将收集一系列的测量，包括药物使用、安全性、情绪、心理社会功能、服药依从性(包括核黄素测试和药片计数)和可卡因渴望的测量。主要的结果衡量标准将是随时间推移的苯甲酰ecGonine的尿毒学结果以及连续三周戒毒的结果。次要结果指标将包括就诊次数、服药依从性、心理社会功能和其他药物使用情况。数据将使用PROC MIX、通用估计方程和参数方差分析方法进行分析。群体规模是基于从其他试验中得出的能量分析，在这些试验中，在这些人群中获得了阳性药物信号。这项研究将提供有关托莫西汀潜在用途的初步安全性和有效性数据，并确定是否有必要进行更大规模的评估。

DESCRIPTION (provided by applicant): This application is written in response to Request for Applications DA-06-002 entitled, "Pilot Clinical Trials of Pharmacotherapies for Substance Related Disorders." Cocaine abuse and dependence has been recognized as a significant public health problem, and no broadly effective medications are available. Recent promising results have been obtained from studies employing the agonist substitution or replacement approach, including studies of d-amphetamine and modafinil. This pilot project proposes to evaluate atomoxetine (Strattera), a compound presently marketed for the treatment of ADHD in adolescents and adults, for the treatment of cocaine dependence. Atomoxetine is a norepinephrine reuptake blocker, which has relatively low affinity for the dopamine and serotonin transport sites. It has been safely tolerated in clinical practice and is associated with low abuse potential. Preliminary data suggest that its pharmacodynamic effects overlap partially with prototypic stimulants, and that maintenance on atomoxetine can reduce the subjective response to cocaine and self-reported ratings of desire for cocaine in cocaine abusing volunteers. This application proposes to conduct a single, placebo-controlled, double blind, randomized pilot clinical trial to evaluate atomoxetine (Stattera) for the treatment of cocaine dependence. Cocaine-dependent healthy individuals, who are seeking treatment for their substance abuse, will be enrolled after careful medical and psychiatric screening to ensure their suitability for the study over a two- week period. Patients will be stratified on variables known to impact cocaine abuse treatment outcomes prior to randomization to one of two groups (n=25/group). Patients will be randomized to receive either atomoxetine (80 mg/day with a brief lead-in) or a matched-placebo during a trial lasting 12 weeks. All patients will participate in weekly cognitive behavioral counseling sessions. A contingency management procedure will be employed to reinforce attendance and decrease attrition from the trial. A broad array of measures, including measures of drug use, safety, mood, psychosocial functioning, and medication compliance (including riboflavin testing and pill counts) and cocaine craving will be collected throughout the course of the trial. The primary outcome measures will be urine toxicology results for benzoylecgonine over time and achievement of three consecutive weeks of abstinence. Secondary outcome measures will include clinic attendance, medication adherence, psychosocial functioning, and other drug use. Data will be analyzed using PROC Mix, General Estimating Equations and parametric ANOVA approaches. The group size was based upon power analyses derived from other trials in which positive medications signals were obtained in this population. This study will provide preliminary safety and efficacy data on the potential utility of atomoxetine and determine whether a larger-scale evaluation is warranted.