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

• 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
• 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

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.

摘要 只有三种药物被食品和药物管理局（FDA）批准用于治疗酒精使用障碍 (AUD)因此迫切需要新的药理学靶点。AUD的特点是失调 酒精的动机和消费，以及影响动机和消费行为的目标可能 保持承诺。一个这样的目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受体广泛表达于奖励相关的脑区和临床前脑区。 GLP-1激动剂，FDA批准用于治疗2型糖尿病和肥胖症，似乎 减少食物和酒精的奖励属性。临床前、人体实验室和 药物流行病学数据表明，GLP-1激动剂对AUD有益，但迄今为止， 一项关于注射用GLP-1激动剂艾塞那肽的试验已经进行;它表明艾塞那肽是最有效的 减少高体重患者的饮酒量。一种特别有前途的GLP-1激动剂，用于治疗AUD 治疗是Semaglutide，其经过优化，可增加血浆活力，与其他药物不同， 配制为皮下注射剂的GLP-1激动剂以口服制剂形式提供。 我们计划在以下治疗组中开展一项探索性随机对照试验（RCT）： 寻找有AUD的人我们将随机分配40名受试者接受semaglutide（滴定至7 mg 每天）或匹配的安慰剂治疗8周。我们的主要目的是评估安全性和耐受性 Semaglutide在该人群中的作用，并评价其相对于安慰剂对酒精线索诱发的渴望的影响 和酒精消费。来自拟议试验的数据将支持随后进行更大规模试验的提议。 Semaglutide口服制剂的RCT。该提案的结果将用于为该大型试验的设计选择提供信息。如果 如果成功，这一系列工作最终可能导致一种新的药物治疗选择的AUD。