CBT and Modafinil for Cocaine Addiction

描述（由申请人提供）：可卡因成瘾是一种破坏性的疾病，破坏个人，家庭和社区，它需要大量的公共卫生资源。独特的成瘾，可卡因依赖和其他兴奋剂依赖没有一个单一的FDA批准的药物。莫达非尼是一种非典型警戒和认知增强剂，在三项人体实验室研究（Dackis et al，2003; Malcolm et al，2006;哈特et al，2007）和一项初步临床试验（Dackis et al，2007）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，对于总体样本（N=203），莫达非尼并不比安慰剂好。事后分析表明，可卡因和酒精共病依赖患者亚群的结果不显著。当合并症组在统计学上被删除时，莫达非尼确实减少了可卡因使用天数，这是通过与安慰剂条件相比的尿液药物筛查验证的（p=0.02）。本次R 01竞争性申报中的受试者人群，沿着四年多来收集的原始数据集，将被单独分析和发表，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发送给FDA。由于临床治疗项目的竞争加剧，以及由于越来越多的受试者患有阿片类药物、其他兴奋剂、处方药和排除性心血管结果的合并症，导致筛选失败率高于预期，因此R 01申请前4年的招募速度放缓。对我们的DSMB进行的设盲无效分析表明信号有希望，需要招募45例额外受试者。这项为期两年的竞争性更新旨在继续采用相同的方法进行本试验，以获得评价疗效和持续监测安全性所需的关键能力。本研究的具体假设仍然是：在寻求治疗的可卡因依赖受试者中，与接受认知行为治疗联合安慰剂的受试者相比，认知行为治疗加口服200 mg或400 mg莫达非尼将具有显著更高的可卡因非使用天数。将通过每周三次定量尿苯唑芽子碱水平确认未使用天数。这项为期两年的竞争性更新的其他目的包括：评估酒精使用对莫达非尼疗效和安全性的影响;对本试验的数据集进行荟萃分析，目前宾夕法尼亚大学的试验，以及最近报道的多中心试验，试图描绘一个受试者亚群，莫达非尼对可卡因依赖的治疗既安全又有效。

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.