An exploratory randomized controlled trial of the effects of oral semaglutide on alcohol craving and consumption

口服索马鲁肽对酒精渴望和消费影响的探索性随机对照试验

基本信息

批准号：
10747743
负责人：
JOSEPH P. SCHACHT
金额：
$ 42.9万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10747743
关键词：
Achievement Acute Acylation Advanced Development Adverse effects Affect Agonist Albumins Alcohol consumption Alcohols Antidiabetic Drugs Area Binding Blood Glucose Body Weight decreased Body mass index Brain Clinical Research Consummatory Behavior Consumption Corpus striatum structure Data Dropout Eating Ethanol Fatty Acids Food Formulation Frequencies GLP-I receptor Gastric Emptying Genes Heavy Drinking Hormone secretion Hospitals Human Hybrids In Vitro Individual Injectable Laboratories Modeling Motivation National Institute on Alcohol Abuse and Alcoholism Non-Insulin-Dependent Diabetes Mellitus Nucleus Accumbens Nutrient Obesity Oral Pancreas Participant Patients Peripheral Pharmaceutical Preparations Pharmacoepidemiology Pharmacological Treatment Pharmacotherapy Phenotype Placebos Plasma Population Pre-Clinical Model Property Publishing Randomized Randomized, Controlled Trials Reporting Research Design Rewards Safety Satiation Schedule Self Administration Sensory Receptors Signal Transduction Small Intestines Stimulus Testing Titrations United States Food and Drug Administration Up-Regulation Variant Ventral Tegmental Area Work alcohol abuse therapy alcohol and other drug alcohol craving alcohol cue alcohol use disorder biological sex chronic alcohol ingestion clinical research site conditioned place preference craving design disorder control disorder risk double-blind placebo controlled trial drinking exenatide gastrointestinal glucagon-like peptide 1 glycemic control hedonic improved insulin secretion liraglutide motivated behavior neural novel peptide hormone pharmacologic pre-clinical pre-clinical research preference prevent programs receptor binding receptor expression response safety assessment subcutaneous treatment duration treatment group trial design

项目摘要

Abstract Only three medications are approved by the Food and Drug Administration (FDA) to treat Alcohol Use Disorder (AUD), and novel pharmacological targets are desperately needed. AUD is characterized by dysregulated motivation for and consumption of alcohol, and targets that affect motivated and consummatory behavior may hold promise. One such target is glucagon-like peptide-1 (GLP-1), a peptide hormone that regulates blood sugar and food intake. GLP-1 receptors are widely expressed in reward-related brain areas, and in preclinical models, GLP-1 agonists, which are FDA-approved for the treatment of Type 2 diabetes and obesity, appear to reduce the rewarding properties of both food and alcohol. Preclinical, human laboratory, and pharmacoepidemiologic data suggest that GLP-1 agonists would be beneficial for AUD, but to date only one trial, of the injectable GLP-1 agonist exenatide, has been conducted; it suggested exenatide was most effective for reducing drinking among patients with higher body mass. A particularly promising GLP-1 agonist for AUD treatment is semaglutide, which is pharmacologically optimized to increase plasma viability and, unlike other GLP-1 agonists that are formulated as subcutaneous injectables, is available in an oral formulation. We propose to conduct an exploratory randomized controlled trial (RCT) of oral semaglutide among treatment- seeking individuals with AUD. We will randomly assign 40 participants to receive semaglutide (titrated to 7 mg per day) or matched placebo for 8 weeks. Our primary aims are to assess the safety and tolerability of semaglutide in this population and to evaluate its effects, relative to placebo, on alcohol cue-elicited craving and alcohol consumption. Data from the proposed trial will support a subsequent proposal to conduct a larger RCT of oral semaglutide. Results from this proposal will be used to inform design choices for this larger trial. If successful, this line of work could ultimately lead to a novel pharmacological treatment option for AUD.

抽象的食品药品监督管理局（FDA）仅批准了三种药物来治疗酒精饮酒障碍（AUD）迫切需要（AUD）和新颖的药理学靶标。 AUD的特征是失调酒精的动机和消费，以及影响动机和完整行为的目标保持诺言。一个靶标是胰高血糖素样肽-1（GLP-1），一种调节血液的肽激素糖和食物摄入量。 GLP-1受体在与奖励相关的大脑区域和临床前广泛表达 FDA批准用于治疗2型糖尿病和肥胖的模型，GLP-1激动剂似乎降低食品和酒精的奖励特性。临床前，人类实验室和药物ePidemiologic数据表明，GLP-1激动剂对AUD有益，但迄今为止只有一个已经进行了可注射的GLP-1激动剂艾鉴定的试验；它建议艾鉴定是最有效的用于减少体重更高的患者的饮酒。 AUD的特别有前途的GLP-1激动剂治疗是半熟肽，在药理学优化以提高血浆生存力的情况下，并且与其他不同口服配方可用为皮下注射剂的GLP-1激动剂。我们建议在处理之间进行口服半卢皮德的探索性随机对照试验（RCT）寻求有声音的人。我们将随机分配40名参与者接受semaglutide（滴定为7 mg 每天）或匹配安慰剂8周。我们的主要目的是评估该人群中的半卢比德，并评估其相对于安慰剂的影响，对酒精提示吸引的渴望和饮酒。拟议试验的数据将支持随后的提案，以进行更大的口服semaglutide的RCT。该提案的结果将用于为这项更大的试验提供为设计选择提供信息。如果成功，这种工作最终可能会导致AUD的新型药理治疗选择。