Zonisamide Treatment of Alcohol Use Disorder: An Evaluation of Efficacy and Mechanism of Action

唑尼沙胺治疗酒精使用障碍：疗效和作用机制评价

基本信息

批准号：
9629630
负责人：
ALBERT JOSEPH ARIAS
金额：
$ 44.36万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9629630
关键词：
Address Aftercare Alcohol dependence Alcoholic beverage heavy drinker Alcoholism American Anticonvulsants Anxiety Attenuated Award Budgets Catchment Area Clinical Research Clinical Trials Complement Connecticut Cues DSM-V Data Collection Effectiveness Face Functional disorder Funding Genes Genetic Polymorphism Genetic Risk Genetic Variation Genetic study Genome Genomics Glean Health Heavy Drinking Impulsivity Individual Knowledge Laboratories Lead Measures Methods Military Personnel Outcome Participant Patients Pattern Pharmaceutical Preparations Pharmacogenetics Pharmacogenomics Pharmacological Treatment Phenotype Pilot Projects Placebos Population Prediction of Response to Therapy Process Randomized Sampling Sertraline Services Stress System Telephone Testing United States National Institutes of Health Universities Veterans Work alcohol abuse therapy alcohol craving alcohol use disorder alcoholism therapy arm attenuation base craving drinking drinking behavior efficacy evaluation endophenotype improved innovation men novel personalized medicine placebo controlled trial predicting response primary outcome psychosocial public health relevance randomized placebo controlled trial recruit research and development stress reactivity topiramate trait treatment effect treatment optimization treatment response

项目摘要

DESCRIPTION (provided by applicant): Zonisamide is an extremely promising anticonvulsant medication for the treatment of alcohol use disorder (AUD). Zonisamide reduces drinking, craving for alcohol, and anxiety in subjects with AUDs. We completed a randomized, placebo-controlled trial of zonisamide for treating alcohol dependence, which showed reductions in heavy drinking, overall drinking, and alcohol craving with the medication. Zonisamide was very well tolerated in the pilot study. Recently, another small placebo-controlled trial of zonisamide showed advantages of the medication over placebo in reducing drinking. However, no definitive study of ZNS treatment for alcoholism has been performed, and there is no such study currently underway in civilians. We have received notice of funding through a Merit Award from the VA Clinical Studies Research and Development (CSR&D) service to conduct a 5-year clinical trial evaluating the efficacy of zonisamide in 160 U.S. Military Veterans with alcoholism. In this R01 application, we propose to add a civilian arm to the study consisting of 160 civilians with Alcohol Use Disorder. Studying the medication's effects in civilians (as well as veterans) will allow us to fully evaluate its efficacy and will make the results more generalizable to the population at large We also propose to add mechanistic and translational components to the combined 320 subject (veteran plus civilian) sample that will allow us to understand better the mechanism of action of zonisamide and other anticonvulsants used to treat alcoholism, as well as help identify observable traits that predict better treatment response. We also propose a novel pharmacogenomic component that adds to the innovation and complements the state-of- the-art trial methods proposed.

描述（由适用提供）：Zonisamide是一种非常有承诺的抗惊厥药，用于治疗酒精使用障碍（AUD）。 Zonisamide可以减少饮酒，渴望酒精以及auds受试者的焦虑。我们完成了一项随机的，安慰剂对照的试验，用于治疗酒精依赖性，该试验显示出大量饮酒，整体饮酒和对药物的酒精渴望的减少。最近，Zonisamide是另一个小安慰剂对照试验的Zonisamide试验，在减少饮酒方面，药物优于安慰剂。但是，尚未对智商治疗酒精中毒进行确定的研究，目前在平民中没有进行此类研究。我们通过VA临床研究研究与开发（CSR＆D）服务获得了一项优点奖，以进行5年临床试验，以评估160名美国有酒精中毒的美国军退伍军人的效率。在此R01申请中，我们建议在该研究中添加一个平民部门，包括160名平民饮酒使用障碍。研究药物在平民（以及退伍军人）中的影响将使我们能够充分评估其有效性，并将使结果更加普遍，我们还建议将机械和翻译的组件添加到320名主题（退伍军人加平民）样本中，这将使我们能够更好地理解Zonisamide和其他用于治疗饮酒的Zonisamide和其他抗惊厥药的作用机理，并有助于确定可预测的特质响应。我们还提出了一种新型的药物基因组成分，该成分增加了创新，并完成了提出的最先进的试验方法。