Evaluation of Atomoxetine for Cocaine Dependence: A Pilot Trial

描述（由申请人提供）：本申请是对申请请求DA-06-002的回应，标题为“物质相关疾病药物治疗的试点临床试验”。可卡因滥用和依赖已被认为是一个重大的公共卫生问题，目前没有广泛有效的药物。最近使用激动剂替代或替代方法的研究获得了有希望的结果，包括对d-安非他明和莫达非尼的研究。这个试点项目建议评估阿托西汀（Strattera），一种目前用于治疗青少年和成人多动症的化合物，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，对多巴胺和血清素转运位点的亲和力相对较低。它在临床实践中是安全耐受的，并且与低滥用可能性有关。初步数据表明，它的药效学作用部分与原型兴奋剂重叠，并且维持阿托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等级。本申请拟进行一项单一、安慰剂对照、双盲、随机的先导临床试验，以评估阿托莫西汀（Stattera）治疗可卡因依赖的效果。正在寻求药物滥用治疗的依赖可卡因的健康个体将在经过仔细的医学和精神筛查后被纳入研究，以确保他们在两周内适合这项研究。患者将根据已知影响可卡因滥用治疗结果的变量进行分层，然后随机分为两组（n=25/组）。在为期12周的试验中，患者将随机接受阿托西汀（80毫克/天，短暂引入）或相匹配的安慰剂。所有患者将参加每周的认知行为咨询会议。将采用应急管理程序来加强出勤并减少试验的人员流失。在整个试验过程中，将收集一系列广泛的措施，包括药物使用、安全性、情绪、社会心理功能、药物依从性（包括核黄素测试和药丸数量）和可卡因渴望。主要结果测量将是随着时间的推移苯甲酰冈碱的尿液毒理学结果和连续三周禁欲的实现。次要结果测量将包括诊所出勤率、药物依从性、心理社会功能和其他药物使用。数据将使用PROC Mix，一般估计方程和参数方差分析方法进行分析。组的大小是基于从其他试验中得出的功率分析，在这些试验中，在这一人群中获得了积极的药物信号。这项研究将提供关于阿托西汀潜在效用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.