CBT and Modafinil for Cocaine Addiction

描述(申请人提供)：可卡因成瘾是一种破坏性的疾病，扰乱个人、家庭和社区，它需要巨大的公共卫生资源。可卡因依赖和其他兴奋剂依赖在成瘾中是独一无二的，没有FDA批准的单一药物。莫达非尼是一种非典型的警示和认知增强剂，在三项人类实验室研究(Dackis等人，2003年；Malcolm等人，2006年；Hart等人，2007年)和一项初步临床试验(Dackis等人，2007年)中显示出治疗可卡因依赖的前景。最近，CPDD报告的一项多中心试验的结果使这些结果变得复杂(Elkashef，2007)。数据表明，对于整个样本(N=203)，莫达非尼并不比安慰剂好。一项事后分析表明，同时依赖可卡因和酒精的患者亚群没有显著结果。当从统计学上排除这一共病组时，莫达非尼确实减少了可卡因的使用天数，与安慰剂组相比，尿药筛查证实了这一点(p=0.02)。本次R01竞争提交的受试者群体，以及四年来收集的原始数据集，将自行进行分析和发表，但它也将成为更大的荟萃分析的一部分，以确定莫达非尼是否将作为可卡因依赖的可能治疗方法被提交给FDA。由于来自临床治疗项目的竞争加剧，以及由于越来越多的受试者合并阿片类药物、其他兴奋剂、处方药和排除性心血管发现而导致的筛查失败率高于预期，这一R01申请的前四年的招募速度有所放缓。为我们的dsmb进行的盲目徒劳分析表明，一个很有希望的信号，需要招募45名额外的受试者。这项为期两年的竞争性续期旨在以相同的方法继续目前的试验，以获得评估疗效和继续监测安全性所需的关键权力。这项研究的具体假设仍然是：在寻求治疗的可卡因依赖者中，与接受认知行为疗法和安慰剂的受试者相比，认知行为疗法加上200毫克或400毫克莫达非尼口服将有明显更多的可卡因不使用天数。未使用日将通过每周三次定量尿苯并促性腺激素水平来确认。这项为期两年的竞争更新的其他目标包括：评估酒精使用对莫达非尼疗效和安全性的影响；对这项试验、当前的宾夕法尼亚大学试验和最近报道的多中心试验的数据集进行荟萃分析，试图描绘出莫达非尼在治疗可卡因依赖方面既安全又有效的受试者亚群。

DESCRIPTION (provided by applicant): Cocaine addiction is a devastating disorder that disrupts individuals, families, and communities, and it requires huge public health resources. Unique among addictions, cocaine dependence and other stimulant dependencies do not have a single FDA-approved medication. Modafinil, an atypical alerting and cognitively enhancing agent, has shown promise for the treatment of cocaine dependence in three human laboratory studies (Dackis et al, 2003; Malcolm et al, 2006; Hart et al, 2007) and in one preliminary clinical trial (Dackis et al, 2007). Those results were recently complicated by the findings from a multi-center trial reported at CPDD (Elkashef, 2007). The data indicated that for the overall sample (N=203), modafinil was no better than placebo. A post hoc analysis indicated that the subpopulation of patients who were comorbidly dependent on cocaine and alcohol had non-significant results. When that comorbid group was statistically removed, modafinil indeed did have a reduction in cocaine use days as validated by urine drug screens when compared to placebo condition (p=0.02). The subject population in this present R01 competitive submission, along with the original data set collected over four years, will be analyzed and published on its own, but it will also become part of a larger meta-analysis to determine whether modafinil will be sent forward to the FDA as a possible treatment for cocaine dependence. Recruitment in the first four years of this R01 application has been slowed by increased competition from clinical treatment programs and from a higher-than-anticipated rate of screen failures due to increasingly more subjects with comorbidities with opiates, other stimulants, prescription medications, and exclusionary cardiovascular findings. A blinded futility analysis conducted for our DSMB indicates a promising signal and the need to recruit 45 additional subjects. This two-year competitive renewal seeks to continue the present trial in its same methodology to gain the critical power necessary to evaluate efficacy and continued monitoring of safety. The specific hypothesis of this study continues to be: in treatment-seeking cocaine dependent subjects, cognitive-behavioral therapy plus 200 mg or 400 mg of modafinil orally will have a significantly higher number of cocaine non-use days as compared to subjects receiving cognitive-behavioral therapy coupled with placebo. Non-use days will be confirmed with three-times-a-week quantitative urine benzolecgonine levels. Additional aims of this two-year competitive renewal include: to evaluate the effects of alcohol use on the efficacy and safety of modafinil; to conduct a meta-analysis of the data set from this trial, the current University of Pennsylvania trial, and the recently reported multi-center trial in an attempt to delineate a subpopulation of subjects for which modafinil is both safe and efficacious for the treatment of cocaine dependence.