MEDICATIONS FOR COCAINE CESSATION /RELAPSE PREVENTION

戒除可卡因/预防复吸的药物

• 批准号: 6933590
• 负责人: JOY Marie SCHMITZ
• 金额: $ 31.58万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6933590
• 关键词: behavior therapy; behavioral /social science research tag; blood chemistry; clinical research; clinical trials; cocaine; combination therapy; craving; data collection methodology /evaluation; drug /alcohol abstinence; drug abuse chemotherapy; drug abuse prevention; drug addiction; drug screening /evaluation; human subject; human therapy evaluation; interview; levodopa; longitudinal human study; naltrexone; outcomes research; psychotherapy; pyrazines; relapse /recurrence; therapy compliance; urinalysis

Cocaine dependence is difficult to treat. Despite more than 40 controlled double-blind trials, no medication has yet been identified as effective for cocaine dependence. To date, most trials have employed heterogeneous samples in terms of baseline level and severity of cocaine use. The possibility exists that certain medications may be more or less effective depending on baseline cocaine use. We propose an innovative methodology that specifies baseline abstinence status a priori, and tests whether this variable moderates the relationship between pharmacotherapy and outcome. In this revised application we have selected three potential medications for which there exists a compelling rationale for examining differential treatment effects under baseline abstinent and nonabstinent conditions. Based on preliminary findings, we hypothesize that naltrexone 50 mg and levodopa/carbidopa 800/200 mg will show significant efficacy over placebo when administered on a baseline of cocaine abstinence, consistent with a "relapse prevention" mechanism. Further, we hypothesize that modafinil 400 mg will show significant efficacy over placebo when administered on a baseline of cocaine non-abstinence, consistent with an "abstinence initiation" mechanism. This 5-year project begins with a 4-week baseline phase involving motivational interviewing and incentive strategies for initiating abstinence in treatment-seeking cocaine users. The second phase of the study consists of a 12-week medication trial comparing four pharmacotherapy conditions (placebo, naltrexone 50mg, levodopa/carbidopa 800/200 mg, and modafinil 400 mg) with stratified random assignment to condition based on baseline abstinence status (abstinent/non-abstinent). During treatment all subjects (N=200) will receive psychotherapy and contingency management designed to enhance medication compliance, with urine screening conducted on a fixed, thrice-weekly schedule. Objective and self-reported drug use will continue to be measured after treatment (3-, 6-months). The assessment battery will capture data necessary to explore secondary aims of the projects, i.e., factors related to achievement of initial abstinence and possible treatment mechanisms by which different medications facilitate cocaine cessation or relapse prevention. Hierarchical multiple regression analyses will be used to determine whether baseline status moderates the effect of pharmacotherapy on outcome. For significant interactions, regression slopes for each treatment condition at the two levels of the moderator (abstinent vs non-abstinent) will be plotted. This project will contribute to our P50 medication development research program by identifying subpopulations and baseline conditions most responsive to treatment, thus providing unique new and valuable information to guide future treatment decision making.

可卡因依赖性很难治疗。尽管有40多个受控双盲试验，但没有 药物尚未被确定为可卡因依赖性。迄今为止，大多数试验都以可卡因使用的基线水平和严重性来采用异质样本。根据可卡因的使用，某些药物可能或多或少有效。我们提出了一种创新的方法，该方法指定了先验基线的禁欲状态，并测试该变量是否缓和了药物治疗与结果之间的关系。在此修订后的应用中，我们选择了三种潜在的药物，其中存在一个令人信服的基本原理，以检查基线戒曲和非固定条件下的差异治疗效果。根据初步发现，我们假设Naltrexone 50 mg和左旋多巴/碳纤维800/200 mg将在可卡因弃权基线上给药时，将对安慰剂显示出明显的功效，与“复发预防”机制一致。此外，我们假设莫达非尼400毫克在可卡因非宽松基线上施用时将显示出对安慰剂的显着疗效，这与“禁欲起始”机制一致。这个为期5年的项目始于为期4周的基线阶段，涉及动机访谈和激励策略，以发起寻求治疗的可卡因使用者。该研究的第二阶段包括一项为期12周的药物试验，该试验比较了四种药物治疗疾病（安慰剂，纳曲酮50mg，levodopa/carbidopa 800/200 mg和modafinil 400 mg），并分层随机分配到基于基于基线的节制状态的条件（原位/非固化）。在治疗期间，所有受试者（n = 200）将接受心理治疗和应急管理 增强药物依从性，以固定的三次时间表进行尿液筛查。治疗后将继续测量客观和自我报告的药物使用（3-1个月）。评估电池将捕获探索项目的次要目标所需的数据，即与实现初始禁欲和可能的治疗机制有关的因素，不同的药物促进可卡因停止或预防复发。分层多元回归分析将用于确定基线状态是否适应药物疗法对预后的影响。对于重要的相互作用，将绘制每个治疗条件的回归斜率在主持人的两个级别上（符合拒绝与非属于非属于的）。该项目将通过确定对治疗的响应最敏感的亚种群和基线状况来为我们的P50药物开发研究计划做出贡献，从而提供独特的新知识信息来指导未来的治疗决策。