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

• 批准号: 8814192
• 负责人: KYLE Matthew KAMPMAN
• 金额: $ 76.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8814192
• 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; Double-blind trial; Drug abuse; Electronic Mail; Enrollment; Ensure; FDA approved; Floor; Frequencies; Functional disorder; Funding; Future; Goals; Health; 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; randomized placebo controlled trial; success; topiramate; transmission process; trial comparing

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）：在美国，可卡因依赖仍然是一个重大的公共卫生问题，并且没有FDA批准的可卡因使用障碍药物治疗。可卡因依赖性的标准社会心理治疗可产生小到中等效应的大小，但对许多可卡因依赖性患者无效。 鉴于近年来在开发有效的酒精，阿片类药物和尼古丁使用障碍的有效药物治疗方面取得了成功，因此开发有效的可卡因使用药物治疗症仍然是重要的公共健康目标。有希望的单独的研究线条表明，苯丙胺和托吡酯是可卡因依赖性的潜在药物疗法，该药物依赖性单独表现出有限的疗效。 这两种药物具有不同的作用机理〜苯丙胺增加了多巴胺的传播，托吡酯降低了伏抗核多巴胺的释放。这种组合可能会降低基线的渴望和可卡因引起的加固。 我们的研究小组进行的一项试点研究（n = 81）发现，混合苯丙胺盐扩展释放（MAS-ER）和托吡酯的组合对于促进可卡因依赖性个体的戒酒有效，尤其是在基线使用率较高的人中。在一项更大的随机安慰剂对照研究中，这种有希望的结果值得确认。 该项目使用PAR-10-099“药物滥用机制的协作临床试验”，该项目是一个两个地点随机双盲试验。我们的目标是研究经常使用可卡因的可卡因依赖性个体，并证明MAS-ER和托吡酯的结合是有效的。该阶段III临床试验的目标是建立 我们有希望的试点研究结果，并检查了使用禁欲定型模型，Mas-ER和托吡酯对可卡因消耗的效果。 具体目的：确定MAS-ER和托吡酯在促进可卡因依赖性患者中戒酒方面的疗效。主要假设：与安慰剂相比，MAS-ER和托吡酯将显着促进可卡因使用的禁欲。主要结局指标将是在试验结束时连续三周可卡因的戒酒，如时间轴遵循的回答方法所记录的，肌酐归一量的定量尿液苯甲酰氨酸（BE）水平证实。次要假设：MAS-ER和托吡酯将1）在研究期间连续三个星期内显着促进戒酒，并且在减少的次数中要优于安慰剂2）2）尿液毒理学样本的比例为〜3）可卡因戒断〜和4）可卡因的症状。我们的研究小组非常适合进行这项研究，因为我们在进行可卡因依赖性药物疗法临床试验方面的丰富经验，并且在使用MAS-ER和托托拉mate治疗可卡因依赖性门诊患者方面具有直接的经验。