Interdisciplinary Study of Two Novel Anticonvulants in Alcoholism

两种新型抗惊厥药治疗酒精中毒的跨学科研究

• 批准号: 8401165
• 负责人: DOMENIC A CIRAULO
• 金额: $ 42.06万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-10 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8401165
• 关键词: Adoption; Advanced Development; Adverse effects; Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Anticonvulsants; Anxiety; Attention; Chemical Structure; Chemicals; Clinical; Clinical Trials; Control Groups; Data; Development; Digit structure; Dose; Double-Blind Method; Effectiveness; Epilepsy; FDA approved; Future; Goals; Health; Heavy Drinking; Human; Impaired cognition; Impairment; Individual; Interdisciplinary Study; Investigation; Levetiracetam; Literature; Measures; Mental Depression; Mind; Modality; Moods; New Agents; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Pharmacologic Actions; Pharmacotherapy; Placebo Control; Placebos; Plasma; Pyrrolidines; Quality of life; Regulation; Relapse; Research Design; Safety; Sampling; Serum; Sleep; Smoking; Sulfonamides; Testing; Time; Toxic effect; Withdrawal Symptom; Word Association Tests; active control; active method; alcohol craving; alcohol use disorder; alcoholism pharmacotherapy; alcoholism therapy; arm; base; carbohydrate-deficient transferrin; clinical practice; cognitive function; comparative; comparative efficacy; drinking; drug efficacy; glutamyltransferase; improved; indexing; innovation; multi-site trial; neurotoxicity; novel; pre-clinical; primary outcome; pyrrolidine; research study; screening; sugar; sulfamate; topiramate

The overarching goal of this study is to build on the results of our pre-clinical and clinical screening experiments of anticonvulsant efficacy and toxicity to guide the development of safer and more effective medications for the treatment of alcohol dependence. This investigation will examine the effects of representative anticonvulsants from three chemical classes: a sugar sulfamate, topiramate; a heterocyclic sulfonamide, zonisamide; and a pyrrolidine, levetiracetam on ethanol consumption and neurotoxicity in alcohol dependent subjects. These medications share some common pharmacologic effects, but also have different actions that are relevant to regulation of ethanol consumption, tolerability, and safety in humans. The primary aim of this proposal is to conduct a double blind placebo controlled parallel group design study with 4 treatment groups (N=40 in each group) in alcohol dependent subjects assigned to receive one of the active study medications or placebo for 14 weeks. We hypothesize that: during the expected period of maximal steady state plasma concentrations, (treatment weeks 10-12), the mean number of drinks per day in each active treatment arm will be significantly lower than in the placebo arm. Furthermore we hypothesize that secondary measures of alcohol consumption and positive clinical outcome in each active treatment arm will show significantly greater efficacy compared to the placebo group. We also hypothesize that subjects in the topiramate group will show greater impairment on a composite measure of neurotoxicity, and tests of verbal fluency and attention than do the other active drug or placebo groups. The immediate benefits of this study will be to help determine if novel anticonvulsants offer safer and more effective alternatives to agents currently approved for the treatment of alcoholism. The broader implications of the study are to guide the selection of existing compounds and the synthesis of new agents for alcoholism treatment based on the chemical classes of the study medications. In turn, this will advance the development of innovative pharmacotherapies for alcohol dependence.

这项研究的总体目标是在我们的临床前和临床结果的基础上 抗惊厥药效和毒性筛选试验指导SAFER的研制 以及更有效的治疗酒精依赖的药物。这项调查将 检查来自三种化学类别的代表性抗惊厥药物的效果：糖类 磺酸托吡酯；杂环磺酰胺；氮磺胺；以及吡咯烷，左乙拉西坦 酒精依赖受试者的酒精消费和神经毒性。这些药物 分享一些共同的药理作用，但也有不同的作用，与 调节人体的乙醇消耗量、耐受性和安全性。这样做的主要目的是 建议进行一项双盲安慰剂对照平行分组设计研究，共4项 酒精依赖受试者中的治疗组(每组40人)被分配接受一次治疗 积极研究的药物或安慰剂，为期14周。我们假设：在 最大稳态血浆浓度的预期时间(治疗周10-12周)， 每个主动治疗组的平均每天饮酒量将显著低于 安慰剂手臂。此外，我们假设酒精消费的次要指标 每个积极治疗组的阳性临床结果将显示出明显更好的疗效 与安慰剂组相比。我们还假设托吡酯组的受试者将 在神经毒性的综合测量和语言流畅性测试中表现出更大的损害 比其他活性药物或安慰剂组更受关注。这样做的直接好处是 研究将帮助确定新型抗惊厥药物是否提供更安全和更有效的 目前批准用于治疗酒精中毒的药物的替代品。更广泛的 这项研究的意义是指导现有化合物的选择和合成 根据研究药物的化学类别开发治疗酒精中毒的新药物。在……里面 反过来，这将促进酒精创新药物疗法的发展 依赖。