Oxytocin Treatment of Alcohol Dependence: A Randomized, Placebo-Controlled Trial

催产素治疗酒精依赖：一项随机、安慰剂对照试验

基本信息

批准号：
8638449
负责人：
James C. Garbutt
金额：
$ 21.85万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-10 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8638449
关键词：
Abstinence Address Admission activity Adverse effects Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcoholic beverage heavy drinker Alcohols Animal Experiments Animal Model Animals Anti-Anxiety Agents Anxiety Back Behavioral Benzodiazepines Brain Clinic Visits Clinical Clinical Trials Collaborations Conduct Clinical Trials Consensus Consumption Dose Double-Blind Method Drops Drug Metabolic Detoxication Effectiveness FDA approved Functional disorder Goals Heavy Drinking Human Inpatients Institutes Intervention Interview Intranasal Administration Lead Lorazepam Measures Medical Methods Modality Moods Morbidity - disease rate Motivation National Institute on Alcohol Abuse and Alcoholism Neuropeptides Neurosciences Nose Outcome Outcome Measure Outpatients Oxytocin Patients Pharmaceutical Preparations Pharmacological Treatment Pilot Projects Placebos Property Publishing Randomized Rattus Relapse Reporting Research Risk Rodent Route Sampling Self-Administered Site Social Behavior Strategic Planning Stress Testing Time Translational Research Withdrawal Withdrawal Symptom alcohol craving alcohol preferring rats biological adaptation to stress coping craving deprivation disability double-blind placebo controlled trial drinking drinking behavior effective therapy experience follow-up hypnotic improved innovation insight interest meetings mental health center mortality primary outcome psychosocial public health relevance randomized placebo controlled trial sedative social cognition standard care trait

项目摘要

DESCRIPTION (provided by applicant): Alcohol dependence (AD) is a major cause of disability, morbidity and mortality world-wide. Current treatment involves various forms of psychosocial treatment and, more recently, pharmacological interventions. However, most patients with AD do not receive treatment and few receive medication, in part because of the modest efficacy of FDA- approved drugs. There is a general consensus that new medications for AD need to be developed that have greater effectiveness and/or new spectrums of activity, e.g. anxiolytic properties. Many recent human studies have found that intranasal administration of oxytocin (OT) has numerous prosocial effects and reduces anxiety. Clinical trials testing high dose intranasal OT for up to 8 weeks found no adverse effects. Several studies indicate that OT may be an effective treatment for AD. Animal experiments have shown that OT blocks tolerance formation to alcohol and markedly decreases withdrawal symptoms. We recently published the results of a randomized, double-blind pilot study in alcohol-dependent subjects undergoing medical detoxification with CIWA score-driven PRN lorazepam treatment. BID intranasal OT was dramatically more effective than placebo in decreasing CIWA scores, the total amount of lorazepam required to complete detoxification, and anxiety measures. Our findings are the first evidence that OT treatment blocks alcohol withdrawal in humans. This is of clinical importance as standard treatment of alcohol withdrawal with benzodiazepines is effective but, unlike OT, may maintain high levels of sedative- hypnotic tolerance that could increase vulnerability to relapse by sustaining alcohol craving, heightened anxiety and diminished ability to cope with stress as well as enabling consumption of large quantities of alcohol upon relapse. We also found that OT administration significantly decreased alcohol consumption and anxiety in P (alcohol-preferring) rats subjected to repeated alcohol deprivation combined with stress, an animal model of relapse. Other animal studies have shown that OT is potently anxiolytic. This evidence suggests that OT treatment may decrease drinking in alcohol- dependent patients by reducing anxiety, vulnerability to stress and perhaps alcohol tolerance. The proposed research represents a unique, translational collaboration between a basic behavioral neuroscientist with expertise in OT (Dr. Cort Pedersen) and an expert in the treatment of AD with extensive experience in conducting clinical trials (Dr. JC Garbutt). We propose a randomized, double-blind, placebo-controlled trial of intranasal OT treatment in 50 alcohol-dependent patients starting early during inpatient medical detoxification and extending for 12 weeks after discharge during which subjects' drinking will be assessed at regular intervals. The overall goal of the project is to determine whether OT treatment in a real world sample of heavy drinkers (patients seeking medical detoxification at a mental health center) is truly effective in decreasing withdrawal symptoms and, in the outpatient setting, reducing drinking. This project has potential to significantly advance the pharmacological treatment of AD. Also, confirming that OT blocks alcohol withdrawal and demonstrating that OT decreases drinking, anxiety, and craving in the outpatient setting would be a triumph of translational research that would establish CNS OT as an important new front for research on the pathophysiology of AD.

描述（由申请人提供）：酒精依赖（AD）是全球残疾，发病率和死亡率的主要原因。当前的治疗涉及各种形式的社会心理治疗以及最近的药理学干预措施。但是，大多数AD患者无法接受治疗，很少接受药物治疗，部分原因是FDA批准的药物的疗效适度。人们普遍的共识是，需要开发具有更大有效性和/或新活动范围的新型AD药物，例如抗焦虑特性。许多最近的人类研究发现，鼻内催产素（OT）具有许多亲社会作用并减轻焦虑。临床试验测试高剂量的鼻内OT长达8周，发现没有不良反应。几项研究表明，OT可能是AD的有效治疗方法。动物实验表明，OT可以阻止对酒精的耐受性形成，并明显减少戒断症状。我们最近发表了一项随机，双盲试验研究的结果，该研究依赖于酒精依赖性受试者，接受了CIWA评分驱动的PRN Lorazepam治疗的医学排毒。在降低CIWA分数，完全排毒所需的Lorazepam总量和焦虑措施中，鼻腔内OT比安慰剂更有效。我们的发现是第一个证据表明，OT治疗会阻止人类在人类中戒酒。这是临床重要性，因为用苯二氮卓类药物对酒精戒断的标准治疗是有效的，但是与OT不同，可能会保持高水平的镇静性催眠耐受性，这可能会增加通过耐心，增强酒精焦虑和减轻压力的能力来增加复发的脆弱性，并在重生中与大量酒精的量化能力以及能够消耗大量酒精。我们还发现，在患有反复的酒精剥夺的P（饮酒）大鼠P（饮酒）大鼠中，OT给药可显着降低酒精消耗和焦虑，加上压力，这是一种复发的动物模型。其他动物研究表明，OT是有效的抗焦虑。该证据表明，OT治疗可能通过减少焦虑，易受压力以及可能的酒精耐受性来减少依赖酒精依赖的患者的饮酒。拟议的研究代表了具有OT专业知识的基本行为神经科学家（Cort Pedersen博士）的独特，转化的合作与在进行临床试验方面具有丰富经验的AD的专家（JC Garbutt博士）。我们提出了一项随机，双盲，安慰剂对照试验的鼻内OT治疗试验，对50名酒精依赖性患者，早期开始在住院医学排毒期间，并在出院后延长12周，在此期间，将定期评估受试者的饮酒。该项目的总体目的是确定在现实世界中，重量饮酒者（在心理健康中心寻求医学排毒的患者）中的OT治疗是否确实有效减少戒断症状，并且在门诊环境中减少饮酒。该项目有可能显着推进AD的药理治疗。同样，确认OT可以阻止酒精的戒断，并证明OT在门诊环境中降低饮酒，焦虑和渴望将是转化研究的胜利，这将确立CNS OT作为AD病理生理学研究的重要新领域。