The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder

多奈哌齐与认知训练相结合治疗酒精使用障碍

• 批准号: 10362148
• 负责人: MORRIS D. BELL
• 金额: $ 47.57万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10362148
• 关键词: Adherence; Aftercare; Age; Alcohol consumption; Alcohols; Alzheimer' s Disease; Back; Brain; Cholinesterase Inhibitors; Clinical; Cognition; Cognitive; Cognitive remediation; Data; Defect; Dendritic Spines; Double-Blind Method; Heavy Drinking; Human; Impaired cognition; Inflammation; Informal Social Control; Inpatients; Intervention; Learning; Measures; Memory; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurocognition; Neurocognitive; Neurocognitive Deficit; Nootropic Agents; Outcome; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase; Pilot Projects; Placebos; Public Health; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recovery; Relapse; Reporting; Research; Short-Term Memory; Testing; Therapeutic Effect; Time; Treatment outcome; United States Food and Drug Administration; alcohol abuse therapy; alcohol craving; alcohol intervention; alcohol use disorder; cholinergic; cognitive benefits; cognitive enhancement; cognitive function; cognitive training; donepezil; drinking; executive function; improved; indexing; mild cognitive impairment; neuron loss; novel; open label; placebo group; psychosocial; treatment adherence; treatment group; trial comparing

Project Summary/Abstract Alcohol use disorder (AUD) is a serious public health problem. Alcohol-related brain defects and alcohol- associated cognitive impairments contribute to the progression of AUD. About 50-80% of patients with AUD have cognitive impairments. These cognitive impairments persist over years and get worse with age. Moreover, alcohol-related cognitive impairments may impact AUD outcomes because executive functions and memory are necessary for self-regulation and learning, which are important during recovery. These cognitive impairments are especially prevalent in the early phase of recovery and reduce the ability to benefit from current AUD treatments. Previous research has suggested that cognitive remediation therapy (CRT) may improve cognitive function and AUD treatment outcomes. There are randomized clinical trials demonstrating that CRT reduces alcohol craving or drinking. However, a few studies also reported that CRT is not effective in reducing drinking. Thus, CRT may need to be augmented by another intervention (e.g., cognitive-enhancing pharmacotherapy) to increase the benefits of CRT. Emerging neurobiological evidence suggests that an anticholinesterase agent donepezil may treat AUD. Donepezil is currently approved by the Food and Drug Administration (FDA) for the treatment of dementia of the Alzheimer's type. Since donepezil has been clinically used as a cognitive enhancer, donepezil may treat AUD while enhancing neurocognitive functioning in patients with AUD. Our pilot data showed that donepezil + CRT might be safe and effective in treating AUD in patients with AUD and mild cognitive impairment. Thus, we here propose a 13-week, randomized, double-blind, placebo-controlled, between-subjects trial comparing 4 groups (donepezil + CRT vs. donepezil alone vs. CRT alone vs. placebos) as a treatment for AUD in a total of 160 patients with AUD. There are two main objectives. Aim #1: To evaluate if donepezil + CRT is superior to placebo in reducing heavy drinking as measured by weekly Time Line Follow Back (TLFB). We hypothesize that donepezil + CRT (group 1) is superior to placebo (group 4) in reducing heavy drinking over 13 weeks of active intervention. We also hypothesize that donepezil alone (group 2) or CRT alone (group 3) is superior to placebo (group 4) in reducing weekly heavy drinking days, and group 1 is superior to groups 2 and 3. Aim #2: To evaluate if donepezil + CRT is superior to placebo in improving global neurocognitive functioning. We hypothesize that donepezil + CRT is superior to placebo in improving global neurocognitive functioning on a global index of neurocognitive function at 7 weeks and at 13 weeks. This project will be the first randomized controlled trial testing donepezil for AUD.

项目摘要/摘要 酒精使用障碍(AUD)是严重的公共卫生问题。与酒精有关的大脑缺陷和酒精- 相关的认知障碍促进了AUD的进展。约50%-80%的AUD患者 有认知障碍。这些认知障碍会持续多年，并随着年龄的增长而恶化。 此外，与酒精相关的认知障碍可能会影响AUD的结果，因为执行功能和 记忆对于自我调节和学习是必要的，而这在恢复过程中是很重要的。这些认知 损伤在恢复的早期阶段尤其普遍，并降低了受益于 目前的AUD治疗。先前的研究表明，认知补救疗法(CRT)可能 改善认知功能和AUD治疗结果。有随机的临床试验证明 这种CRT可以减少饮酒欲望或饮酒。然而，一些研究也报告说，CRT在 减少饮酒。因此，可能需要通过另一种干预(例如，认知增强)来增强CRT 药物治疗)，以增加CRT的益处。新出现的神经生物学证据表明， 抗胆碱酯酶药物多奈哌齐可治疗AUD。多奈哌齐目前已获美国食品药品监督管理局批准 美国食品和药物管理局(FDA)用于治疗阿尔茨海默病类型的痴呆症。因为多奈哌齐已经在临床上 作为一种认知增强剂，多奈哌齐可以在治疗AUD的同时增强患者的神经认知功能 用澳元。我们的初步数据显示，多奈哌齐联合CRT治疗AUD安全有效。 患有澳门氏症和轻度认知障碍。因此，我们在这里提出了为期13周的随机、双盲、 安慰剂对照的受试者间试验，比较4组(多奈哌齐+CRT与多奈哌齐单独与CRT 作为AUD的一种治疗方法，共有160名AUD患者。 有两个主要目标。 目的#1：评估多奈哌齐+CRT在减少大量饮酒方面是否优于安慰剂 每周时间线回溯(TLFB)。我们假设多奈哌齐+CRT(第1组)优于安慰剂 (4)积极干预13周以上减少重度饮酒。我们还假设多奈哌齐 单独(第2组)或CRT单独(第3组)在减少每周大量饮酒方面优于安慰剂(第4组 天数，组1优于组2和组3。 目的#2：评估多奈哌齐+CRT在改善全球神经认知功能方面是否优于安慰剂。 我们假设多奈哌齐+CRT在改善全球神经认知功能方面优于安慰剂。 7周和13周神经认知功能的全球指数。 该项目将是第一个测试多奈哌齐治疗AUD的随机对照试验。