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）依赖性在美国的许多地区普遍存在。这种疾病的重要后遗症包括认知障碍，乙型肝炎和C和HIV感染。认知障碍和戒断症状，​​例如，嗜睡，疲劳和渴望，可能会使用户处于复发的危险中。没有既定的药物疗法来依赖MA。莫达非尼是一种新型的启动唤醒药物，可缓解疲劳，增强认知功能，耐受性良好并且滥用责任低。莫达非尼直接可卡因的主观效应，减少可卡因在门诊患者中的使用，并且我们小组最近完成的工作表明，与静脉内MA共同管理时，它是安全的。将进行一项为期8周的剂量范围研究，以评估莫达非尼在治疗MA依赖性方面的效果。 MA依赖受试者将被随机分配为每天接收200或400 mg的莫达非尼或安慰剂。评估将包括用于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，苯丙胺戒断问卷，血浆莫达非尼水平，血液化学水平，血液化学水平和不良事件报告。一种自我报告和尿液毒理学复合度量的广义估计方程模型，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血浆浓度与结果之间的关系。我们假设1）莫达非尼将是安全且容忍良好的，2）给定400 mg莫达非尼的人将使用比给定安慰剂的人使用的MA更少，而3）PK/PD建模将揭示莫达非尼水平和a）认知功能之间的浓度效应关系，a）认知症状，b戒断症状，​​以及c）MA的使用。