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: 8506141
• 负责人: Robert James Malcolm
• 金额: $ 37.34万
• 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 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8506141
• 关键词: Abstinence; Acetylcysteine; Adherence; Adolescent; Adverse event; Age; Alcohol dependence; American; Animal Model; Animals; Basic Science; Behavior; Brain; Cardiovascular system; Chronic; Cigarette; Clinic; Clinic Visits; Clinical Data; 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; Homeostasis; Human; Incentives; Individual; Informed Consent; Laboratory Study; Manuals; Marijuana Smoking; Measures; Methods; Monitor; Outcome Measure; Outpatients; Patient Self-Report; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Phase; Placebo Control; Placebos; Pregnancy Outcome; 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; animal data; base; cocaine exposure; cocaine relapse prevention; cocaine use; 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 study; programs; public health relevance; 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，以评估N-乙酰半胱氨酸(NAC)作为预防复发药物治疗可卡因依赖的疗效。寻求治疗的可卡因依赖男性和女性，年龄18至70岁，所有族裔和种族背景，将获得知情同意，并筛选令人满意的纳入和排除标准。这项研究有两个可行的假设。首先，NAC将根据一组可卡因依赖者在开始用药前被确认戒除至少7天的复吸时间的多个事件间隔衡量标准，减少对可卡因的复吸。其次，在停药后的4周随访期内，NAC组将显示出比安慰剂更持久的疗效。研究NAC治疗可卡因成瘾疗效的理论基础最初是基于动物数据，这些数据表明，长期接触可卡因后，谷氨酸能大脑回路受到干扰。NAC能改善谷氨酸能缺陷，抑制可卡因和线索诱导的可卡因寻找行为的恢复。最近的临床前工作有力地表明，在短暂的可卡因戒断之后，NAC将是一种最有效的复发预防药物。在动物中，这些积极影响在NAC停止后持续数周。在进入我们最近的NAC试验并禁欲几天的一小部分受试者中，我们的两种NAC治疗剂量都显示出比安慰剂更长的复发时间。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。将对知情同意后经UDS确认戒酒的潜在受试者进行筛查。在第一阶段，受试者将进入为期一周的开放标签安慰剂阶段，继续监测禁欲，促进坚持每天服用两次开放标签安慰剂，并前往诊所就诊。在第二阶段，受试者将被随机分组，以平衡性别、共病酒精依赖、吸烟状况和过去30天内基线可卡因使用(或11天使用)的严重程度。为了验证假设一，受试者将参加为期八周的试验，每天服用1200毫克NAC两次或同等外观和气味的安慰剂，为期八周，每周三次诊所就诊。激励措施将 针对服药依从性和门诊就诊。受试者将接受认知行为疗法(CBT)，这是一种标准化的手动支持性心理疗法，经常用于成瘾药物试验。多项事件发生时间指标将绘制出八周内的禁欲存活率分析。为了验证假设二，NAC将在第八周结束时停止，受试者将每周再回来一个月。据我们所知，NAC作为预防人类可卡因成瘾的复发药物的有效性尚未得到评估。