Evaluation of Atomoxetine for Cocaine Dependence: A Pilot Trial

托莫西汀对可卡因依赖性的评估：初步试验

• 批准号: 7172881
• 负责人: Sharon L. Walsh
• 金额: $ 36.63万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-26 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7172881
• 关键词: clinical research; cocaine

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.

描述（由申请人提供）：本申请是为了响应申请要求DA-06-002的题为“针对物质相关疾病的药物治疗的试验临床试验”。可卡因滥用和依赖已被认为是一个重大的公共卫生问题，并且没有广泛有效的药物可用。通过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，获得了最新的有希望的结果。该试点项目提议评估阿托莫西汀（Strattera），这是一种目前销售用于青少年和成年人的多动症的化合物，用于治疗可卡因依赖性。阿托西汀是一种去甲肾上腺素的再摄取阻滞剂，对多巴胺和5-羟色胺转运位点的亲和力相对较低。它在临床实践中被安全耐受，并且与低虐待潜力有关。初步数据表明，其药物动力学作用部分与原型刺激剂重叠，并且对原子氨酸的维持可以减少对可卡因的主观反应，并自我报告的可卡因渴望的可卡因渴望的渴望等级。该申请建议进行一项单一的，安慰剂对照的，双盲，随机的试验临床试验，以评估阿托西汀（Stattera）以治疗可卡因依赖性。可卡因依赖的健康个体正在寻求治疗毒品的治疗，将在仔细的医学和精神病学筛查后被招募，以确保他们在两周内对研究的适用性。患者将在已知会影响可卡因滥用治疗结果的变量上进行分层，然后随机分为两组之一（n = 25/组之一）。在持续12周的试验中，将随机分配患者接受阿托莫西汀（短暂介入）或匹配的位置。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增强出勤率并减少试验的损耗。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，心情，社会心理功能和药物合规性（包括核黄素测试和药丸计数）和可卡因渴望。主要结局指标将是随着时间的推移和连续三周的禁欲而实现苯甲酰链氨酸的尿液毒理学结果。次要结果指标将包括诊所出勤，药物依从性，社会心理功能和其他药物使用。将使用PROC混合，一般估计方程和参数方差分析方法对数据进行分析。该组的规模基于从其他试验中得出的功率分析，在该试验中，该人群在该人群中获得了阳性药物信号。这项研究将提供有关原子石潜在效用的初步安全性和有效性数据，并确定是否保证了大规模评估。