Zonisamide for the Treatment of Alcohol Use Disorder in the Addiction Neuroclinical Assessment Framework

唑尼沙胺用于治疗成瘾神经临床评估框架中的酒精使用障碍

基本信息

批准号：
10665706
负责人：
Sterling M McPherson
金额：
$ 63.59万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10665706
关键词：
Address Adherence Adult Adverse event Alcohol Phenotype Alcohol consumption Alcohols Alzheimer&apos s Disease Animals Anticonvulsants Behavior Bibliotherapy Biochemical Clinical Trials Community Health Data Devices Disulfiram Double-Blind Method Emotional Executive Dysfunction FDA approved Glucuronides Glutamates Goals Health Heavy Drinking Heterogeneity Human Hypertension Impaired cognition Incentives Individual Laboratories Learning Liver Cirrhosis Malignant Neoplasms Measures Mediator Mental Depression Naltrexone Odds Ratio Outcome Pancreatitis Participant Patient Self-Report Patients Pharmaceutical Preparations Pharmacotherapy Placebo Control Placebos Population Primary Care Primary Health Care Public Health Randomized Risk Safety Severities Single-Blind Study Stroke Testing Time Titrations Urine Visit acamprosate addiction adherence rate alcohol abuse therapy alcohol measurement alcohol seeking behavior alcohol use disorder biological sex cognitive function contingency management cost design drinking efficacy evaluation emotional functioning experience follow-up improved incentive salience medication compliance new technology novel point of care primary care setting primary outcome prospective randomized placebo-controlled clinical trial randomized, clinical trials recruit reduced alcohol use secondary outcome sound standard care tool treatment duration treatment group treatment response two-arm trial

项目摘要

PROJECT SUMMARY/ABSTRACT Alcohol use disorder (AUD) is an alarming public health problem that costs the US more than $249 billion annually. AUDs leads to a devastatingly diverse set of negative health outcomes, including significantly increased risk of hypertension, stroke, pancreatitis, liver cirrhosis, Alzheimer’s disease, multiple cancers, and multiple types of cognitive dysfunction. Disulfiram, naltrexone, and acamprosate are the only FDA-approved medications for the treatment of AUD and are only modestly effective. Zonisamide (ZON) is an anticonvulsant medication with GABAnergic, glutamatergic and monoaminergic effects which has shown significant promise in animal and human laboratory settings, and small clinical trials for the treatment of AUD. ZON could represent a critical new tool for clinicians, but previous studies have been limited by a couple of key factors (e.g., no objective evidence recent alcohol consumption, no objective evidence of medication adherence) that this study is designed to overcome. Theoretically framed within the Addiction Neuroclinical Assessment with hypothesized mechanisms in core domains (i.e., incentive salience, negative emotionality and cognitive function), and proceeding from a sound scientific premise we will target reduced alcohol use among AUD patients in primary care using a carefully designed combination of contingency management (CM, or incentives in exchange for objectively verified evidence of behavior) delivered at thrice-weekly visits during the first 4- weeks of ZON treatment to jumpstart reductions in drinking. For the remaining 8-weeks of ZON, CM will be delivered at weekly visits in exchange for evidence of 100% or higher medication adherence. The goal of this study is to complete a double-blind, placebo-controlled RCT to evaluate the ability of ZON to significantly decrease alcohol use among treatment-seeking AUD adults. Individuals will be randomized into 1 of 2 trial arms that will receive: 1) ZON plus standard treatment (ST), which includes Take Control bibliotherapy modules and CM through the 12-week treatment period (ZON+ST), or 2) Matched placebo plus ST (PLO+ST). The primary outcome will be biochemically-verified alcohol use during the treatment period. We will use a 2-week, single- blind placebo induction period wherein participants will be required to demonstrate a 75% medication adherence rate before continuing into the 12-week treatment period. Follow-up will occur at 1, 6 and 12-months. Our Specific Aims are to: 1) Determine if ZON+ST is more effective than PLO+ST for reducing biochemically- verified alcohol use and other alcohol use outcomes; 2) Identify ANA-based mediators of treatment response across the treatment groups; 3) Determine a.) if biological sex, baseline depression and baseline severity of alcohol use interacts with treatment assignment to produce differential changes in our primary and secondary outcomes; and b.) whether groups differ on adverse events or medication adherence. This project focuses on the efficacy of a promising pharmacotherapy for AUDs using a double-blind placebo-controlled design that will rigorously measure alcohol use and medication adherence.

项目概要/摘要酒精使用障碍 (AUD) 是一个令人担忧的公共卫生问题，给美国造成的损失超过 2,490 亿美元每年澳元都会导致一系列毁灭性的负面健康后果，其中包括显着的后果。患高血压、中风、胰腺炎、肝硬化、阿尔茨海默病、多种癌症的风险增加双硫仑、纳曲酮和阿坎酸是唯一获得 FDA 批准的药物。用于治疗 AUD 的药物，唑尼沙胺 (ZON) 是一种抗惊厥药，效果有限。具有 GABA 能、谷氨酸能和单胺能作用的药物，已显示出巨大的前景在动物和人类实验室环境中，治疗 AUD 的小型临床试验可以代表。对于忠实的人来说这是一个重要的新工具，但之前的研究受到几个关键因素的限制（例如，没有近期饮酒的客观证据，没有服药依从性的客观证据）表明本研究旨在克服成瘾神经临床评估的理论框架。核心领域的压力机制（即激励显着性、消极情绪和认知函数），并从合理的科学前提出发，我们的目标是减少澳元的饮酒量使用精心设计的应急管理组合（CM 或激励措施）对初级保健中的患者进行治疗以换取客观验证的行为证据），在前 4 周期间每周三次访问 ZON 治疗周开始减少饮酒在 ZON 的剩余 8 周内，CM 将进行。每周访视一次，以换取 100% 或更高的药物依从性的证据。研究的目的是完成一项双盲、安慰剂对照的随机对照试验，以评估 ZON 显着改善疗效的能力减少寻求治疗的 AUD 成年人的饮酒量，个体将被随机分为 2 个试验组中的 1 个。将接受： 1) ZON 加标准治疗 (ST)，其中包括 Take Control 阅读治疗模块和 CM 至 12 周治疗期 (ZON+ST)，或 2) 匹配安慰剂加 ST (PLO+ST)。结果将是在治疗期间经过生化验证的酒精使用情况，我们将使用为期 2 周的单次酒精治疗。盲目安慰剂诱导期，参与者将被要求证明 75% 的药物治疗继续 12 周治疗期之前的依从率将在 1、6 和 12 个月时进行。我们的具体目标是： 1) 确定 ZON+ST 是否比 PLO+ST 更有效地减少生化- 验证酒精使用和其他酒精使用结果；2) 确定基于 ANA 的治疗反应调节因素； 3) 确定 a.) 是否存在生物性别、基线抑郁症和基线严重程度酒精使用与治疗分配的相互作用使我们的小学和中学产生不同的变化结果；和 b.) 各组在不良事件或药物依从性方面是否存在差异。使用双盲安慰剂对照设计的一种有前途的 AUD 药物疗法的疗效将严格测量饮酒和药物依从性。