2/2 Multicenter trial of combined pharmacotherapy to treat cocaine dependence

2/2 联合药物疗法治疗可卡因依赖的多中心试验

基本信息

批准号：
8639514
负责人：
KYLE Matthew KAMPMAN
金额：
$ 77.54万
依托单位：
UNIVERSITY OF PENNSYLVANIA
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：
2013-04-01 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8639514
关键词：
Abstinence Address Adult Alcohols Amphetamines Back Binding Sites Clinical Trials Cocaine Cocaine Dependence Combination Medication Communities Consumption Corpus striatum structure Creatinine Data Data Analyses Development Discipline Disease Dopamine Double-Blind Method Drug abuse Electronic Mail Enrollment Ensure FDA approved Floor Frequencies Functional disorder Funding Future Goals Incentives Individual Medical Methods Modeling Multicenter Trials National Institute of Drug Abuse Nicotine Use Disorder Nucleus Accumbens Opioid Outcome Outcome Measure Outpatients Participant Patient Self-Report Patients Pennsylvania Pharmaceutical Preparations Pharmacotherapy Phase III Clinical Trials Pilot Projects Placebos Population Positioning Attribute Procedures Psychological reinforcement Public Health Randomized Recruitment Activity Research Research Design Salts Sampling Signal Transduction Site Symptoms Telephone Testing Therapeutic Therapeutic Effect Time TimeLine Toxicology Treatment outcome United States Universities Urine Visit Withdrawal Withdrawal Symptom Work arm benzoylecgonine cocaine use collaborative trial community based practice craving economic cost evidence base experience medication compliance meetings pilot trial placebo controlled study primary outcome psychosocial public health relevance randomized placebo controlled trial success topiramate transmission process trial comparing

项目摘要

DESCRIPTION (provided by applicant): Cocaine dependence continues to be a significant public health problem in the United States and there are no FDA-approved pharmacotherapies for cocaine use disorders. Standard psychosocial treatments for cocaine dependence yield small-to-medium effect sizes, but are not effective for many cocaine-dependent patients. Given the success in recent years in developing effective pharmacotherapies for alcohol, opioid, and nicotine use disorders, the development of effective pharmacotherapies for cocaine use disorders remains an important public health goal. Promising separate developing lines of research suggest that amphetamine and topiramate are potential pharmacotherapies for cocaine dependence that individually have demonstrated limited efficacy. These two medications have distinct mechanisms of action~ amphetamine increases dopamine transmission and topiramate reduces nucleus accumbens dopamine release. This combination may decrease baseline craving and cocaine-induced reinforcement. A pilot study (N=81) conducted by our research group found that the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate was effective for promoting abstinence among cocaine- dependent individuals, particularly among those with a greater frequency of use at baseline. This promising result warrants confirmation in a larger randomized placebo-controlled study. Using the PAR-10-099 "Collaborative Clinical Trials in Drug Abuse" mechanism, the proposed project is a two site randomized double- blind trial. We aim to study cocaine-dependent individuals who use cocaine frequently and for whom the combination of MAS-ER and topiramate was shown to be effective. The goal of this phase III clinical trial is to build on our promising pilot study results and examine the efficacy of the combination of MAS-ER and topiramate on cocaine consumption using an abstinence-initiation model. Specific Aim: To determine the efficacy of MAS-ER and topiramate in promoting cocaine abstinence among cocaine-dependent patients. Primary Hypothesis: MAS-ER and topiramate will significantly promote abstinence from cocaine use as compared to placebo. The primary outcome measure will be three consecutive weeks of cocaine abstinence at the end of the trial as recorded by the Timeline Follow-Back method confirmed by creatinine-normalized quantitative urine benzoylecgonine (BE) levels. Secondary Hypotheses: MAS-ER and topiramate will 1) significantly promote abstinence during any three consecutive weeks during the study period and be superior to placebo in reducing 2) the proportion of urine toxicology samples negative for BE~ 3) symptoms of cocaine withdrawal~ and 4) cocaine craving. Our research group is well suited to conduct this study given our extensive experience in conducting cocaine dependence pharmacotherapy clinical trials, as well as having direct experience in using MAS-ER and topiramate to treat cocaine-dependent outpatients.

描述（由申请人提供）：可卡因依赖在美国仍然是一个重大的公共卫生问题，并且 FDA 没有批准针对可卡因使用障碍的药物疗法。针对可卡因依赖的标准心理社会治疗产生小到中等的效果，但对许多可卡因依赖患者无效。鉴于近年来在开发针对酒精、阿片类药物和尼古丁使用障碍的有效药物疗法方面取得的成功，开发针对可卡因使用障碍的有效药物疗法仍然是一个重要的公共卫生目标。有希望的单独发展研究表明，安非他明和托吡酯是治疗可卡因依赖的潜在药物疗法，但各自的疗效有限。这两种药物具有不同的作用机制——安非他明增加多巴胺的传递，托吡酯减少伏隔核多巴胺的释放。这种组合可能会减少基线渴望和可卡因引起的强化。我们的研究小组进行的一项试点研究（N = 81）发现，混合安非他明盐缓释剂（MAS-ER）和托吡酯的组合可有效促进可卡因依赖者的戒断，特别是那些频率较高的人在基线时使用。这一有希望的结果值得在更大规模的随机安慰剂对照研究中得到证实。拟议项目采用 PAR-10-099“药物滥用合作临床试验”机制，是一项两中心随机双盲试验。我们的目标是研究经常使用可卡因的可卡因依赖者，并且 MAS-ER 和托吡酯的组合对他们来说是有效的。这项 III 期临床试验的目标是建立在我们有希望的试点研究结果，并使用戒断启动模型检查 MAS-ER 和托吡酯组合对可卡因消耗的功效。具体目标：确定 MAS-ER 和托吡酯在促进可卡因依赖患者戒除可卡因方面的功效。主要假设：与安慰剂相比，MAS-ER 和托吡酯将显着促进可卡因的戒断。主要结果指标是试验结束时连续三周的可卡因戒断情况，通过时间线追踪方法记录，并通过肌酐标准化定量尿苯甲酰爱康宁 (BE) 水平进行确认。次要假设：MAS-ER 和托吡酯将 1) 在研究期间的任何连续三周内显着促进戒断，并且在减少 2) 尿液毒理学样本 BE 阴性的比例~ 3) 可卡因戒断症状~和方面优于安慰剂。 4）对可卡因的渴望。鉴于我们在进行可卡因依赖药物治疗临床试验方面的丰富经验，以及使用 MAS-ER 和托吡酯治疗可卡因依赖门诊患者的直接经验，我们的研究小组非常适合开展这项研究。