Haass-Koffler Carolina L, Kashyap Bhavani, Gully Brian J, Nambiar Sithara S, Hornbacher Rivkah, Foster Stephanie L, Silberman Yuval, Swift Robert M, Hanson Leah R, Frey William H
Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Contemp Clin Trials Commun. 2025 Jun 10;46:101509. doi: 10.1016/j.conctc.2025.101509. eCollection 2025 Aug.
Despite developments in treatments for alcohol use disorder (AUD), current pharmacotherapies face several limitations, including adverse events. Intranasal (IN) insulin has shown promise for addictive disorders. The overarching hypothesis of this trial is that by increasing brain cell energy and glucose metabolism, while reducing stress hormones, IN insulin may be an ideal approach for treating multiple domains of AUD including memory, executive function and impulsivity. Preclinical and clinical studies of IN insulin demonstrate that it is a safe and effective method for delivering insulin to the central nervous system, circumventing the blood brain barrier, and reducing adverse events associated with insulin use (hypoglycemia). The overarching goal of this Phase I/IIa, within-subject, crossover, double-blind, placebo-controlled, alcohol interaction trial is to test the IN insulin (80IU), compared to placebo (0.9 % saline) as a potential therapy for AUD. The primary aim assesses the safety and tolerability of IN insulin, compared to placebo, in individuals with AUD ( = 40) who are not currently seeking treatment. The secondary aim assesses the safety and tolerability of IN insulin, compared to placebo, when co-administered with alcohol (0.08 g/dL). Tertiary aims include assessing cognitive performance, memory, and impulsivity following IN insulin, or placebo, and alcohol administration. Finally, an alcohol cue reactivity procedure investigates the effect of IN insulin, compared to placebo, in alcohol craving. This is the first study to evaluate IN insulin in an AUD population and this manuscript describes the rationale, design, and methodology of the alcohol interaction trial. This study is designed to accelerate research for the development of novel medications to treat AUD and provide empirical evidence on the safety and efficacy of a neurotherapeutic approach to inform clinical practice.
NCT05988632.
FDA/IND: 168417.
尽管酒精使用障碍（AUD）的治疗取得了进展，但目前的药物治疗仍面临一些局限性，包括不良事件。鼻内（IN）胰岛素已显示出对成瘾性疾病的治疗前景。本试验的总体假设是，通过增加脑细胞能量和葡萄糖代谢，同时降低应激激素，IN胰岛素可能是治疗AUD多个方面（包括记忆、执行功能和冲动性）的理想方法。IN胰岛素的临床前和临床研究表明，它是一种将胰岛素输送到中枢神经系统、绕过血脑屏障并减少与胰岛素使用相关的不良事件（低血糖）的安全有效方法。本I/IIa期、受试者内、交叉、双盲、安慰剂对照、酒精相互作用试验的总体目标是测试IN胰岛素（80IU）与安慰剂（0.9%生理盐水）相比作为AUD潜在治疗方法的效果。主要目的是评估IN胰岛素与安慰剂相比，在目前未寻求治疗的AUD个体（n = 40）中的安全性和耐受性。次要目的是评估IN胰岛素与安慰剂相比，与酒精（0.08 g/dL）共同给药时的安全性和耐受性。三级目的包括评估IN胰岛素或安慰剂以及酒精给药后对认知表现、记忆和冲动性的影响。最后，一项酒精线索反应程序研究IN胰岛素与安慰剂相比对酒精渴望的影响。这是第一项在AUD人群中评估IN胰岛素的研究，本手稿描述了酒精相互作用试验的原理、设计和方法。本研究旨在加速开发治疗AUD的新型药物的研究，并为一种神经治疗方法的安全性和有效性提供实证证据，为临床实践提供参考。
NCT05988632。
FDA/IND：168417。
