Clinical assessment of ivermectin as a therapeutic agent to reduce alcohol intake

伊维菌素作为减少酒精摄入量治疗剂的临床评估

基本信息

批准号：
8924767
负责人：
Megan Marie Yardley
金额：
$ 4.28万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
2014-08-19 至 2016-04-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8924767
关键词：
Acute Address Affect Aftercare Alcohol abuse Alcohol consumption Alcohol dependence Alcohol-Related Disorders Alcoholic Beverages Alcoholism Alcohols Anti-Anxiety Agents Antiparasitic Agents Attenuated Behavioral Paradigm Benzodiazepines Biological Assay Case-Control Studies Cessation of life Chronic Clinical Clinical Research Clinical Trials Clinical assessments Cognitive Competence Development Dose Employment Enrollment FDA approved Fellowship Fostering Glass Goals Health Heavy Drinking Hour Human Individual Investigation Ivermectin Laboratories Marble Measures Modeling Motor Mus National Research Service Awards Oral Participant Patient Self-Report Patients Pharmaceutical Preparations Pharmacotherapy Placebo Control Placebos Property Questionnaires Randomized Regimen Reporting Research Personnel Research Proposals Rewards Rodent Safety Scientist Self Administration Sensory Severe Adverse Event Smell Perception Testing Therapeutic Therapeutic Agents Time Toxic effect Training Translating Water addiction alcohol craving alcohol effect alcohol use disorder base biobehavior cost cue reactivity drinking drug development experience novel novel therapeutics pre-clinical preclinical study preference primary outcome research study tool treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Despite considerable efforts focusing on new drug development to reduce alcohol abuse, high rates of harmful drinking persist. Thus, developing novel therapeutics for the treatment of alcohol use disorders (AUDs) is of paramount importance. Defining novel drug therapies, using existing approved drugs for other indications, represents an economically feasible, fast approach for drug development. This training proposal is based on preclinical studies showing that acute and chronic administration of ivermectin (IVM) reduces alcohol intake and preference in mice without eliciting overt signs of toxicity. As IVM is currently FDA-approved and used by millions of humans each year for other indications, its novel employment to reduce alcohol intake opens an exciting new venue in the quest for new drugs to treat AUDs. Human laboratory models are an especially useful tool in effectively translating preclinical findings and elucidating the biobehavioral mechanisms by which pharmacotherapies may be efficacious for alcohol dependence (AD). The objective of this NRSA application is to foster my development as a clinical/ translational researcher focusing on medications development for alcoholism. The proposed study will test the hypothesis that IVM decreases alcohol consumption by evaluating the effects of this medication on an alcohol self-administration task in non-treatment seeking individuals with AD. Specifically, Aim 1 tests the hypothesis that IVM will attenuate alcohol self-administration in non- treatment seeking individuals with AD. Aim 2 tests the hypothesis that IVM will dampen alcohol craving using cue reactivity (CR) assessment. The present study represents an important step in: 1) the implementation of IND enabling studies that will satisfy a portion of the FDA requirements for the development of IVM as a new indication for treatment of AUDs and 2) my scientific development and maturity as an independent clinical/ translational alcohol researcher.

描述（由申请人提供）：尽管大量努力着重于新药开发以减少酗酒，但有害饮酒率仍然存在。因此，开发用于治疗酒精使用障碍（AUD）的新型治疗剂至关重要。使用现有批准的药物来定义新型药物疗法代表了经济上可行的，快速的药物开发方法。该培训建议基于临床前研究表明，急性和长期给药伊维菌素（IVM）可减少小鼠的酒精摄入量和偏爱，而不会引起明显的毒性迹象。由于目前，IVM每年被FDA批准并被数百万人类用于其他适应症，因此其减少酒精摄入量的新型就业机会为寻求新药物治疗auds的新场地打开了一个令人兴奋的新场地。人类实验室模型是有效地翻译临床前发现和阐明药物治疗可能有效饮酒（AD）的生物行为机制的特别有用工具。 NRSA应用的目的是促进我作为一名专注于酒精中毒的临床/转化研究人员的发展。拟议的研究将检验以下假设：IVM通过评估这种药物对酒精自我管理任务的影响，从而减少酒精消耗，以寻求AD的人。具体而言，目标1检验了以下假设：IVM将减弱在寻求AD患者的非治疗中的酒精自我管理。 AIM 2检验了以下假设：IVM将使用提示反应性（CR）评估抑制酒精的渴望。本研究是：1）实施IND促进研究的重要步骤，该研究将满足IVM发展的一部分FDA要求，以作为治疗AUDS的新指示； 2）我作为独立的临床/翻译酒精研究人员的科学发展和成熟度。