N-acetylcysteine for Relapse Prevention to Cocaine Use

N-乙酰半胱氨酸用于预防可卡因吸毒复发

• 批准号: 9012052
• 负责人: Robert James Malcolm
• 金额: $ 37万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-15 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9012052
• 关键词: Abstinence; Acetylcysteine; Adherence; Adolescent marijuana use; Age; Alcohol dependence; American; Animal Model; Animals; Basic Science; Behavior; Brain; Cardiovascular system; Chronic; Cigarette; Clinic; Clinic Visits; Clinical Data; Clinical Research; Clinical Trials; Clinical Trials Design; Cocaine; Cocaine Dependence; Cognitive Therapy; Controlled Clinical Trials; Counseling; Cues; Data; Databases; Dose; Double-Blind Method; Drug usage; Equilibrium; Event; Exclusion Criteria; Exposure to; FDA approved; Female; Gambling; Gender; Glutamates; Goals; HIV Infections; Health; Homeostasis; Human; Incentives; Individual; Informed Consent; Laboratory Study; Manuals; Measures; Methods; Monitor; Outcome Measure; Outpatients; Patient Self-Report; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Phase; Placebo Control; Placebos; Prevention trial; Prostitution; Psychotherapy; Publishing; Randomized; Randomized Clinical Trials; Recruitment Activity; Relapse; Reporting; Research; Research Design; Research Personnel; Rewards; Risk; Role; Sampling; Severities; Signal Transduction; Smell Perception; Smoking Status; Staging; Subgroup; Survival Analysis; Testing; Time; Unsafe Sex; Work; addiction; adverse pregnancy outcome; animal data; base; brain circuitry; cocaine exposure; cocaine relapse prevention; cocaine use; cognitive control; cost; craving; disorder later incidence prevention; double-blind placebo controlled trial; experience; follow-up; inclusion criteria; male; medication compliance; open label; pill; pre-clinical; preclinical trial; programs; racial and ethnic; research study; sugar; week trial

DESCRIPTION (provided by applicant): This application proposes a double-blind clinical trial to evaluate the efficacy of N-acetylcysteine (NAC) as a relapse prevention agent for the treatment of cocaine dependence. Treatment-seeking cocaine dependent males and females, ages 18 to 70 and of all ethnic and racial backgrounds, will be given informed consent and screened for satisfactory inclusion and exclusion criteria. The study has two working hypotheses. First, NAC will decrease relapse to cocaine use, based on multiple time-to-event measures of relapse in a group of cocaine-dependent individuals with at least 7 days of confirmed abstinence from cocaine before medication initiation. Second, the NAC group will show sustained efficacy over placebo in the 4-week follow-up period after medication is discontinued. The rationale for investigating the efficacy of NAC in the treatment of cocaine addiction was initially based on animal data that pointed to perturbations of glutamatergic brain circuitry after chronic operant exposure to cocaine. NAC ameliorated glutamatergic deficits and inhibited cocaine and cue induced reinstatement of cocaine seeking behaviors. Recent preclinical work strongly suggests that NAC will be most effective as a relapse prevention agent after a brief period of abstinence from cocaine. In animals, these positive effects persist for several weeks after cessation of NAC. In a small subset of subjects entering our recent NAC trial with a few days of abstinence, both of our NAC treatment doses showed substantially longer times to relapse than placebo. We will recruit subjects being treated for cocaine dependence in two similar intensive outpatient programs. Potential subjects with UDS-confirmed abstinence after informed consent will be screened. In Stage 1, subjects will enter a one week open-label placebo phase to continue to monitor abstinence and promote adherence to taking open-label placebo twice daily and attend clinic visits. In Stage 2, subjects will be "urn" randomized to balance for gender, co-morbid alcohol dependence, smoking status and severity of baseline cocaine use (< or >11 days use) in the past 30 days. To test hypothesis one, subjects will participate in an eight week trial of 1200 mg of NAC twice daily or equal-appearing and smelling placebo twice daily for eight weeks with three clinic visits per week. Incentives will be directed at medication adherence and clinic attendance. Subjects will attend cognitive behavior therapy (CBT), a standardized manual driven supportive psychotherapy frequently used in addiction medication trials. Multiple time-to-event measures will plot abstinence survival analyses over the eight weeks. To test hypothesis two, NAC will be discontinued at the end of week eight and subjects will return weekly for one additional month. To our knowledge, NAC has not been evaluated for efficacy as a relapse prevention medication for cocaine addiction in humans.

描述（由申请人提供）：本申请提出了一项双盲临床试验，以评价N-乙酰半胱氨酸（NAC）作为治疗可卡因依赖的复发预防剂的疗效。寻求治疗的可卡因依赖男性和女性，年龄18至70岁，所有种族和人种背景，将获得知情同意书，并筛选符合入选和排除标准的患者。这项研究有两个工作假设。首先，NAC将减少可卡因使用的复发，这是基于一组可卡因依赖个体的复发的多个时间-事件测量，这些个体在开始用药前至少有7天证实戒断可卡因。其次，NAC组在停药后的4周随访期内将显示出相对于安慰剂的持续疗效。 研究NAC治疗可卡因成瘾疗效的基本原理最初是基于动物数据，这些数据表明慢性操作性暴露于可卡因后多巴胺能脑回路的扰动。NAC改善了可卡因能缺陷，抑制可卡因和线索诱导的可卡因寻求行为的恢复。最近的临床前研究强烈表明，NAC将是最有效的复发预防剂后，从可卡因短暂的禁欲期。在动物中，这些积极的影响持续数周后停止NAC。在最近进入我们的NAC试验的一小部分受试者中，禁欲几天，我们的两种NAC治疗剂量显示复发时间比安慰剂长得多。 我们将在两个类似的强化门诊项目中招募正在接受可卡因依赖治疗的受试者。将筛选知情同意后经UDS证实戒烟的潜在受试者。在第1阶段，受试者将进入为期一周的开放标签安慰剂期，以继续监测禁欲并促进对每日两次服用开放标签安慰剂的依从性，并参加临床访视。在第2阶段，受试者将被随机分配至性别、共病酒精依赖、吸烟状态和过去30天内基线可卡因使用（使用11天）的严重程度的平衡< or >。为了检验假设一，受试者将参加为期八周的试验，每天两次服用1200 mg NAC或每天两次服用外观和气味相同的安慰剂，持续八周，每周三次门诊。激励措施将针对药物依从性和诊所出勤率。受试者将参加认知行为疗法（CBT），这是一种经常用于成瘾药物试验的标准化手册驱动的支持性心理疗法。多个事件发生时间指标将绘制八周内的禁欲生存分析。为了检验假设二，NAC将在第八周结束时停用，受试者将每周返回一次，持续一个月。据我们所知，NAC尚未被评估作为人类可卡因成瘾复发预防药物的有效性。