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

基本信息

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
项目类别：
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

项目摘要

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）作为治疗可卡因依赖的复发预防剂的功效。寻求治疗的可卡因依赖男性和女性，年龄在 18 岁至 70 岁之间，不分种族和种族背景，将获得知情同意，并进行筛选，以确定是否符合纳入和排除标准。该研究有两个可行的假设。首先，NAC 将减少可卡因使用的复发，这是基于对一组可卡因依赖者的复发时间进行的多项测量，这些人在开始用药前至少 7 天确认戒除可卡因。其次，在停药后 4 周的随访期内，NAC 组将显示出相对于安慰剂的持续疗效。研究 NAC 在治疗可卡因成瘾方面的功效的基本原理最初是基于动物数据，这些数据表明长期操作性接触可卡因后谷氨酸能大脑回路会受到干扰。 NAC 改善谷氨酸能缺陷并抑制可卡因和提示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，在短暂戒除可卡因后，NAC 作为预防复发的药物将是最有效的。在动物中，这些积极作用在停止 NAC 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接受可卡因依赖治疗的受试者。将筛选在知情同意后经 UDS 确认禁欲的潜在受试者。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，以继续监测禁欲情况并促进坚持每天两次服用开放标签安慰剂并参加诊所就诊。在第 2 阶段，受试者将被随机分配，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严重程度（<或>11 天使用）。为了检验假设一，受试者将参加一项为期八周的试验，每天两次服用 1200 毫克 NAC，或每天两次服用外观和气味相同的安慰剂，为期八周，每周三次就诊。激励措施将针对药物依从性和就诊情况。受试者将参加认知行为疗法（CBT），这是一种标准化的手动驱动的支持性心理疗法，经常用于成瘾药物试验。多种事件发生时间测量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止，受试者将每周返回一个月。据我们所知，NAC 作为人类可卡因成瘾预防复发药物的功效尚未得到评估。