CBT and Modafinil for Cocaine Addiction

CBT 和莫达非尼治疗可卡因成瘾

基本信息

批准号：
7648230
负责人：
Robert James Malcolm
金额：
$ 36.69万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7648230
关键词：
Adverse effects Adverse event Alcohol consumption Alcohol dependence Alcohols Anterior Hypothalamus Attention deficit hyperactivity disorder Blinded Cardiovascular system Clinical Clinical Treatment Clinical Trials Clinical Trials Data Monitoring Committees Cocaine Cocaine Dependence Communities Comorbidity Conduct Clinical Trials Coupled Data Data Set Dependency Disease Dopamine Uptake Inhibitors Drug Addiction Electrocardiogram Enrollment Ensure Excessive Daytime Sleepiness FDA approved Failure Family Futility Glutamates Health Resources Histamine Human Individual Laboratories Laboratory Study Link Major Depressive Disorder Manuals Measures Meta-Analysis Methodology Modafinil Monitor Multicenter Trials National Institute of Drug Abuse Neurocognitive Neurons Norepinephrine Opiates Patient Self-Report Patients Pennsylvania Pharmaceutical Preparations Phase Physical assessment Placebos Population Preclinical Drug Evaluation Psychological reinforcement Psychosocial Factor Public Health Publishing Randomized Recruitment Activity Reporting Riboflavin Safety Sampling Serotonin Agonists Signal Transduction Site Sleep Disorders Time Treatment outcome Universities Upper arm Urine addiction carbohydrate-deficient transferrin cocaine use cognitive behavior therapy design efficacy testing extracellular hypocretin preclinical study randomized placebo controlled trial treatment program

项目摘要

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.

描述（由申请人提供）：可卡因成瘾是一种破坏个人，家庭和社区的毁灭性疾病，需要大量的公共卫生资源。在成瘾中，可卡因依赖性和其他兴奋剂依赖性在成瘾中独有的依赖性没有单一的FDA批准药物。莫达非尼是一种非典型警报和认知增强的剂，在三项人类实验室研究中显示了可卡因依赖性的希望（Dackis等，2003; Malcolm等，2006; Hart等，2007）和一项初步的临床试验（ Dackis等，2007）。最近在CPDD报道的多中心试验的发现中，这些结果变得复杂（Elkashef，2007年）。数据表明，对于整体样本（n = 203），莫达非尼不比安慰剂好。事后分析表明，依赖可卡因和酒精的患者的亚群体的亚群效果不大。当该合并症组被统计去除时，与安慰剂条件相比，莫达非尼确实确实减少了可卡因使用天数（p = 0.02）。本本R01竞争提交中的主题人群以及四年来收集的原始数据集将被单独分析和发布，但它也将成为更大的荟萃分析的一部分，以确定是否会向前发送莫达非尼将FDA作为可卡因依赖性的可能治疗方法。由于临床治疗计划的竞争增加以及越来越多的筛查率率增加了，由于越来越多的受试者与阿片类药物，其他兴奋剂，处方药以及排他性的受试者，在此R01应用程序的前四年招聘已经减缓了筛查率的竞争减慢。心血管发现。对我们的DSMB进行的盲目徒劳分析表明，有希望的信号，并且需要招募45名其他受试者。这项为期两年的竞争性更新旨在以相同的方法继续进行本试验，以获得评估安全性和继续监视安全所需的关键能力。这项研究的具体假设仍然是：在寻求可卡因的受试者中，认知行为疗法加上200 mg或400 mg的莫达非尼口服的可卡因非使用天数明显更高。行为疗法与安慰剂结合。无用的日子将以每周三倍的定量尿液苯甲酰氨酸水平确认。这两年竞争性更新的其他目的包括：评估饮酒对莫达非尼疗效和安全性的影响；为了对本试验，现任宾夕法尼亚大学试验的数据集进行荟萃分析，以及最近报道的多中心试验，试图描述莫达非尼对莫达非尼对治疗的受试者的亚群来划定。可卡因依赖性。