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请求 DA-06-002，题为“物质相关疾病药物疗法的试点临床试验”。可卡因滥用和依赖已被认为是一个重大的公共卫生问题，并且没有广泛有效的药物。最近采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-苯丙胺和莫达非尼的研究。该试点项目旨在评估托莫西汀（Strattera）（一种目前上市用于治疗青少年和成人多动症的化合物）对可卡因依赖的治疗效果。阿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。它在临床实践中已被安全耐受，并且滥用可能性较低。初步数据表明，其药效作用与原型兴奋剂部分重叠，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对可卡因的渴望评级。本申请拟进行一项单一、安慰剂对照、双盲、随机试点临床试验，以评估托莫西汀（Stattera）治疗可卡因依赖的效果。因药物滥用而寻求治疗的可卡因依赖健康个体将在经过仔细的医学和精神病学筛查后入组，以确保他们适合参加为期两周的研究。在随机分入两组中的一组（n=25/组）之前，将根据已知影响可卡因滥用治疗结果的变量对患者进行分层。在持续 12 周的试验中，患者将被随机分配接受阿托莫西汀（80 毫克/天，短暂导入）或匹配的安慰剂。所有患者将参加每周一次的认知行为咨询课程。将采用应急管理程序来提高出勤率并减少试验人员流失。在整个试验过程中，将收集一系列广泛的指标，包括药物使用、安全、情绪、心理社会功能和药物依从性（包括核黄素测试和药丸计数）以及可卡因渴望的指标。主要结果指标是苯甲酰爱康宁随时间推移的尿液毒理学结果以及连续三周的禁欲情况。次要结果指标包括门诊就诊率、用药依从性、心理社会功能和其他药物使用情况。将使用 PROC Mix、一般估计方程和参数方差分析方法来分析数据。小组规模是基于其他试验得出的功效分析，在这些试验中，在该人群中获得了积极的药物信号。这项研究将提供有关阿托莫西汀潜在用途的初步安全性和有效性数据，并确定是否需要进行更大规模的评估。