A dose ranging study of modafinil for methamphetamine dependence

描述(申请人提供)：甲基苯丙胺(MA)依赖在美国许多地区很普遍。这种疾病的重要后遗症包括认知障碍、乙型和丙型肝炎以及艾滋病毒感染。认知障碍和戒断症状，例如嗜睡、疲劳和渴望，可能会使使用者面临复发的风险。对于MA依赖，目前还没有确定的药物治疗方法。莫达非尼是一种新型的促醒剂，具有缓解疲劳、增强认知功能、耐受性好、滥用倾向低的特点。莫达非尼减弱了可卡因的主观影响，减少了门诊患者的可卡因使用，我们小组最近完成的研究表明，与静脉注射MA联合给药是安全的。将进行为期8周的剂量范围研究，以评估莫达非尼治疗MA依赖的效果大小。MA依赖的受试者将被随机分配为每天接受200或400毫克的莫达非尼或安慰剂。评估将包括MA的尿检、MA使用的自我报告、成瘾严重程度指数、艾滋病行为的风险、神经认知测试组合、苯丙胺戒断问卷、血浆莫达非尼水平、血液化学和不良事件报告。使用自我报告和尿毒理学综合测量的广义估计方程模型来评估莫达非尼剂量对MA使用的影响。药代动力学/药效学(PK/PD)模型将用于确定莫达非尼血药浓度和结果之间的关系。我们假设1)莫达非尼将是安全和耐受性良好的，2)服用400毫克莫达非尼的人将比服用安慰剂的人使用更少的MA，3)PK/PD模型将揭示莫达非尼水平与a)认知功能、b)戒断症状和c)MA使用之间的浓度-效应关系。

DESCRIPTION (provided by applicant): Methamphetamine (MA) dependence is prevalent in many regions of the United States. Important sequelae of this illness include cognitive impairment, hepatitis B and C, and HIV infection. Cognitive impairment and withdrawal symptoms, e.g., somnolence, fatigue, and craving, may put users at risk for relapse. There is no established pharmacotherapy for MA dependence. Modafinil is a novel wake-promoting agent that relieves fatigue, enhances cognitive function, is well tolerated, and has low abuse liability. Modafinil blunts the subjective effects of cocaine, reduces cocaine use in outpatients, and recently completed work by our group indicates that it is safe when co-administered with intravenous MA. An 8-week dose ranging study will be conducted to assess the effect size of modafinil for treatment of MA dependence. MA dependent subjects will be randomly assigned to receive either 200 or 400 mg per day of modafinil or placebo. Assessments will include urinalysis for MA, self-report of MA use, the Addiction Severity Index, the Risk for AIDS Behaviors, a neurocognitive test battery, the Amphetamine Withdrawal Questionnaire, plasma modafinil levels, blood chemistries, and adverse event reports. A generalized estimating equation model of a composite measure of self-report and urine toxicology be used to assess the effect of modafinil dose on MA use. Pharmacokinetic/pharmacodynamic (PK/PD) modeling will used to determine the relationship between modafinil plasma concentration and outcomes. We hypothesize that 1) modafinil will be safe and well tolerated, 2) persons given 400 mg modafinil will use less MA than those given placebo, and 3) PK/PD modeling will reveal concentration-effect relationships between modafinil levels and a) cognitive function, b) withdrawal symptoms, and c) MA use.