An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence

纳曲酮加阿立哌唑治疗酒精依赖的探索性研究

基本信息

批准号：
7595229
负责人：
RAYMOND F ANTON
金额：
$ 16.45万
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：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7595229
关键词：
Abstinence Acute Address Admission activity Adopted Adverse effects Adverse event Affect Alcohol abuse Alcohol dependence Alcohols American Anxiety Brain Burn Units Clinical Clinical Trials Combination Medication Combined Modality Therapy Controlled Clinical Trials Data Dependence Development Diabetes Mellitus Dopamine Dose Dropout Drug Combinations Evaluation Evidence based treatment FDA approved Functional Magnetic Resonance Imaging Goals Health Expenditures Health Professional Heavy Drinking Hypertension Individual Intensive Care Laboratories Life Medical Medicine Moods Naltrexone Narcotic Antagonists New Agents Nurses Outcome Outpatients Pathway interactions Pharmaceutical Preparations Pharmacotherapy Physicians Pilot Projects Placebo Control Placebos Play Property Psychological reinforcement Psychotic Disorders Randomized Recruitment Activity Relapse Research Research Project Grants Role Safety Sample Size System Testing Work addiction alcohol abuse therapy alcohol cue alcohol research alcoholism therapy animal data aripiprazole automobile accident cost craving depression dopamine system drinking experience improved medication compliance neurochemistry neuroimaging primary outcome problem drinker productivity loss programs treatment duration treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Our group has gained considerable experience in the conduct of sophisticated pharmacotherapy trials with naltrexone, and other medications, in alcohol dependent individuals. While naltrexone has found utility in the treatment of this condition, there is considerable room for improvement, since it does not work for everyone. One way to potentially enhance naltrexone's efficacy is to combine it with another medication having a unique pharmacological profile. Similar combination therapy approaches have been found useful in a number of medical conditions (e.g. hypertension, diabetes, depression). Differing from naltrexone, aripiprazole is an FDA approved medication for the treatment of psychotic disorders which works by stabilizing the dopamine system, a neurochemical system known to play a large role in reinforcement and addiction. Our experience with the use of aripiprazole in a clinical trial with alcoholics, during a sub-acute dosing and bar-lab study with neuroimaging in non-treatment seeking alcoholics, and from animal data, suggests that it would be a good medication to combine with naltrexone for treatment-seeking alcohol dependent individuals. Aripiprazole is well-tolerated and safe in actively drinking individuals, and also lacks many of the more serious adverse effects shown by medications working on brain dopamine (e.g., extrapyramidal effects and dyskinisias). As a prelude to this proposal, we have found aripiprazole to be well tolerated when combined with naltrexone in a small pilot study. While data collected so far indicate tolerability of this combination, further data are needed to explore the potential safety and efficacy of combining aripiprazole with naltrexone. Therefore, in this exploratory/pilot study, we propose to randomize 60 alcohol dependent individuals to receive either naltrexone, naltrexone plus aripiprazole, or their matching placebos over a 16-week treatment period. All individuals will receive 9 sessions of Medical Management as developed for the COMBINE Study. The primary outcome variable will be drinks per drinking day. Heavy drinking days, clinical global outcome, craving, compliance, adverse events, mood and other variables will also be assessed to evaluate the effects of the medication combination over naltrexone alone. If this medication combination is found effective in this exploratory study, a larger clinical trial will be planned.

描述（由申请人提供）：我们的小组在对酒精依赖个体进行纳曲酮和其他药物的复杂药物治疗试验方面获得了丰富的经验。虽然纳曲酮已在治疗这种疾病方面发挥了作用，但仍有很大的改进空间，因为它并不适合所有人。潜在增强纳曲酮功效的一种方法是将其与另一种具有独特药理学特征的药物结合使用。类似的联合治疗方法已被发现可用于治疗许多疾病（例如高血压、糖尿病、抑郁症）。与纳曲酮不同，阿立哌唑是 FDA 批准的用于治疗精神障碍的药物，其通过稳定多巴胺系统起作用，多巴胺系统是一种已知在强化和成瘾中发挥重要作用的神经化学系统。我们在酗酒者临床试验中使用阿立哌唑的经验、在非治疗寻求酗酒者中进行的亚急性剂量和酒吧实验室神经影像学研究以及动物数据表明，这将是一种很好的药物组合纳曲酮用于寻求治疗的酒精依赖者。阿立哌唑对于经常饮酒的人具有良好的耐受性和安全性，并且也没有作用于大脑多巴胺的药物所表现出的许多更严重的副作用（例如锥体外系效应和运动障碍）。作为该提案的前奏，我们在一项小型试点研究中发现阿立哌唑与纳曲酮联合使用时具有良好的耐受性。虽然迄今为止收集的数据表明该组合的耐受性，但需要进一步的数据来探索阿立哌唑与纳曲酮组合的潜在安全性和有效性。因此，在这项探索性/试点研究中，我们建议随机抽取 60 名酒精依赖者，在 16 周的治疗期内接受纳曲酮、纳曲酮加阿立哌唑或其匹配的安慰剂。所有个人都将接受为 COMBINE 研究开发的 9 次医疗管理课程。主要结果变量是每个饮酒日的饮酒量。还将评估大量饮酒天数、临床总体结果、渴望、依从性、不良事件、情绪和其他变量，以评估药物组合相对于单独纳曲酮的效果。如果在这项探索性研究中发现这种药物组合有效，将计划进行更大规模的临床试验。