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: 8055873
• 负责人: GANTT P GALLOWAY
• 金额: $ 51.13万
• 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 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8055873
• 关键词: Acetamides; Acquired Immunodeficiency Syndrome; Address; Adverse event; Amphetamines; Behavior; Blood Chemical Analysis; Central Nervous System Stimulants; Clinical; Clinical Trials; Cocaine; Cocaine Dependence; Conduct Clinical Trials; Dose; Drowsiness; Drug Kinetics; Equation; FDA approved; Fatigue; HIV Infections; Hepatitis B; Hepatitis C; Impaired cognition; Industry; Intravenous; Investigation; Measures; Methamphetamine; Methamphetamine dependence; Methylphenidate; Modafinil; Modeling; Outcome; Outpatients; Patient Self-Report; Patients; Pemoline; Persons; Pharmaceutical Preparations; Pharmacotherapy; Placebo Control; Placebos; Plasma; Population; Questionnaires; Randomized; Relapse; Reporting; Risk; Safety; Sampling; Severities; Sleep Disorders; Thinking; Toxicology; United States; Urinalysis; Urine; Withdrawal; Withdrawal Symptom; Work; abstracting; addiction; cocaine use; cognitive function; craving; design; drug development; experience; improved; indexing; neurocognitive test; novel; pharmacodynamic model; pharmacokinetic model; pill; randomized trial; simulation; sugar; trial comparing; vigilance

Project Summary/Abstract 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. Project Narrative Methamphetamine addiction is a serious problem in the United States for which no medications have been shown to be helpful. Modafinil is a medication that is used to treat sleep disorders, has shown promise as a cocaine addiction treatment, and may help the withdrawal and difficulty thinking that methamphetamine users have when quitting. We will conduct a randomized trial of placebo (sugar pill) and two doses of modafinil to see which dose is most useful in treating methamphetamine-addicted outpatients.

项目总结/摘要 甲基苯丙胺（MA）依赖在美国的许多地区都很普遍。严重后遗症 这种疾病包括认知障碍、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， 缓解疲劳、增强认知功能、耐受性好，并且具有低滥用倾向。莫达非尼使 可卡因的主观影响，减少门诊患者的可卡因使用，以及我们小组最近完成的工作 表明与静脉MA联合给药时是安全的。 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的效应量 依赖MA依赖性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的尿液分析、MA使用的自我报告、成瘾严重程度 指数，艾滋病行为的风险，神经认知测试电池，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复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）建模将 用于确定莫达非尼血药浓度与结局之间的关系。我们假设 1）莫达非尼是安全的，耐受性良好，2）服用400 mg莫达非尼的患者使用的MA比服用400 mg莫达非尼的患者使用的MA少。 3）PK/PD建模将揭示莫达非尼水平之间的浓度-效应关系 和a）认知功能，B）戒断症状，和c）MA使用。项目叙述 甲基苯丙胺成瘾在美国是一个严重的问题， 没有任何药物显示出有帮助。莫达非尼是一种 用于治疗睡眠障碍，已显示出作为可卡因成瘾的前景 治疗，并可能有助于戒断和困难的想法， 冰毒使用者戒烟时的症状我们将进行一项随机试验 安慰剂（糖丸）和两个剂量的莫达非尼，看看哪一个剂量是最 可用于治疗甲基苯丙胺成瘾的门诊患者。