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

• 批准号: 10456903
• 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
• 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/10456903
• 关键词: Address; Adherence; Adult; Adverse event; Alcohol Phenotype; Alcohol consumption; Alcohols; Alzheimer' 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 of activation protein; Mental Depression; Naltrexone; Odds Ratio; Outcome; Pancreatitis; Participant; Patient Rights; Patient Self-Report; Patients; Pharmaceutical Preparations; Pharmacotherapy; Placebo Control; Placebos; Population; Primary Health Care; Public Health; Randomized; Randomized Clinical Trials; 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; base; biological sex; cognitive function; contingency management; cost; design; drinking; 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; recruit; reduced alcohol use; secondary outcome; sound; standard care; tool; treatment duration; treatment group; treatment response; two-arm trial

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.

项目摘要/摘要 酒精使用障碍（AUD）是一个令人震惊的公共卫生问题，耗资超过2490亿美元 单程。 AUDS导致一系列毁灭性的负面健康结果，包括显着 高血压，中风，胰腺炎，肝硬化，阿尔茨海默氏病，多种癌症的风险增加 多种类型的认知功能障碍。二硫仑，纳曲酮和Appamprosate是唯一的FDA批准 用于治疗AUD的药物仅适度有效。 Zonisamide（ZON）是一种抗惊厥药 用GABAN能，谷氨酸能和单胺能作用的药物，这表现出了巨大的希望 在动物和人类实验室环境中，以及用于治疗AUD的小型临床试验。 Zon可以代表 对于临床医生来说，这是一个关键的新工具，但以前的研究受到了两个关键因素的限制（例如，否 目的证据最近的饮酒，没有客观的药物依从性证据）这项研究 旨在克服。理论上在成瘾的神经临床评估中构造了 核心领域的假设机制（即激励显着性，负面情绪和认知 功能），并从一个合理的科学前提开始，我们将针对AUD中的饮酒减少 使用应急管理（CM或激励措施）精心设计的初级保健患者 为了换取明显验证的行为证据），在第4--期间进行三次访问。 几周的ZON处理以开始减少饮酒。对于剩余的8周的Zon，CM将是 每周访问以换取100％或更高药物依从性的证据。目标的目标 研究是要完成双盲，安慰剂对照的RCT，以评估Zon的能力显着 减少寻求治疗的AUD成年人中的酒精使用。个人将被随机分为2个试用武器中的1个 将会收到：1）ZON PLUS标准处理（ST），其中包括对控制书籍疗法模块和 CM至12周的治疗期（ZON+ST），或2）匹配的安慰剂加ST（PLO+ST）。主要 在治疗期间，结果将是生化验证的饮酒。我们将使用2周的单一 盲人安慰剂诱导期，将要求参与者证明75％的药物 继续进入12周的治疗期之前。随访时间为1、6和12个月。 我们的具体目的是：1）确定Zon+ST是否比PLO+ST更有效，以减少生化 - 经过验证的饮酒和其他酒精使用结果； 2）确定基于ANA的治疗反应的介体 在整个治疗组中； 3）确定a。）是否生物学性别，基线抑郁和基线严重程度 酒精使用与治疗分配相互作用，以在我们的初级和次级中产生差异变化 结果；和b。）群体在不良事件或药物依从性方面是否有所不同。这个项目重点 使用双盲安慰剂对照设计的有前途的药物疗法的有前途的药物治疗的效率 严格测量的酒精使用和药物依从性。