A dose ranging study of modafinil for methamphetamine dependence

莫达非尼治疗甲基苯丙胺依赖的剂量范围研究

• 批准号: 7467416
• 负责人: GANTT P GALLOWAY
• 金额: $ 50.76万
• 依托单位: CALIFORNIA PACIFIC MED CTR RES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7467416
• 关键词: Acetamides; Acquired Immunodeficiency Syndrome; Address; Adverse event; Amphetamines; Behavior; Blood Chemical Analysis; Central Nervous System Stimulants; Clinical; Clinical Trials; Cocaine; Conduct Clinical Trials; Dependence; Dose; Drowsiness; Drug Kinetics; Equation; Fatigue; HIV Infections; Hepatitis B; Impaired cognition; Industry; Intravenous; Investigation; Measures; Methamphetamine; Methylphenidate; Modafinil; Modeling; Numbers; Outcome; Outpatients; Patient Self-Report; Patients; Pemoline; Personal Satisfaction; Persons; Pharmacodynamics; Pharmacotherapy; Placebo Control; Placebos; Plasma; Population; Questionnaires; Randomized; Range; Rate; Relapse; Reporting; Risk; Safety; Sampling; Severities; Sleep Disorders; Standards of Weights and Measures; Toxicology; United States; United States Food and Drug Administration; Urinalysis; Urine; Week; Withdrawal; Withdrawal Symptom; Work; addiction; cognitive function; craving; day; design; drug development; experience; improved; indexing; neurocognitive test; novel; pharmacodynamic model; pharmacokinetic model; simulation; size; trial comparing; vigilance

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.

描述（由申请人提供）：甲基苯丙胺（MA）依赖在美国许多地区普遍存在。这种疾病的重要后遗症包括认知障碍、B和C型肝炎以及HIV感染。认知障碍和戒断症状，例如，嗜睡、疲劳和渴望可能使使用者处于复发的风险中。没有确定的药物治疗MA依赖。莫达非尼是一种新型促醒剂，可缓解疲劳，增强认知功能，耐受性良好，滥用倾向低。莫达非尼减弱了可卡因的主观效应，减少了门诊患者的可卡因使用，我们小组最近完成的工作表明，与静脉注射MA联合使用时是安全的。将进行一项为期8周的剂量范围研究，以评估莫达非尼治疗MA依赖的效应量。MA依赖受试者将被随机分配接受200或400 mg/天的莫达非尼或安慰剂。评估将包括MA的尿分析、MA使用的自我报告、成瘾严重程度指数、艾滋病行为风险、神经认知测试组合、安非他明戒断问卷、血浆莫达非尼水平、血液化学和不良事件报告。自我报告和尿液毒理学综合测量的广义估计方程模型可用于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浆浓度和结局之间的关系。我们假设：1）莫达非尼是安全的，耐受性良好; 2）给予400 mg莫达非尼的患者使用的MA少于给予安慰剂的患者; 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。