Alcoholic Hepatitis Clinical and Translational Network Late Phase Clinical Trials and Observational Studies 9/9

酒精性肝炎临床和转化网络后期临床试验和观察研究 9/9

• 批准号: 10887713
• 负责人: ARUN J SANYAL
• 金额: $ 11.67万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10887713
• 关键词: Adrenal Cortex Hormones; Alcoholic Hepatitis; Alcoholic Liver Diseases; Alcohols; Biological Specimen Banks; Caring; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Collection; Conduct Clinical Trials; Consumption; Data Coordinating Center; Data Set; Databases; Development; Disease; Economic Burden; Educational workshop; Eligibility Determination; Foundations; Funding; Future; Goals; Grant; Granulocyte Colony-Stimulating Factor; Infection; Inflammasome; Inflammation; Informatics; Interleukin-1 Receptors; Interleukin-1 beta; Label; Laboratories; Learning; Life; Literature; Liver; Liver diseases; Medical; Mission; Morbidity - disease rate; National Institute on Alcohol Abuse and Alcoholism; Observational Study; Oral cavity; Outcome; Pathogenesis; Patient Care; Patient Recruitments; Patients; Pentoxifylline; Pharmaceutical Preparations; Phase; Pilot Projects; Positioning Attribute; Predisposition; Prednisone; Public Health; Randomized; Research Design; Research Personnel; Resources; Role; Sampling; Severities; Systems Biology; Testing; Therapeutic; Therapeutic Studies; Translational Research; Validation; Work; Zinc; active method; anakinra; antagonist; clinical center; clinical trial recruitment; drug testing; effective therapy; efficacy trial; end stage liver disease; evidence base; improved; insight; interest; liver injury; longitudinal database; meetings; mortality; new therapeutic target; novel; prednisolone; primary endpoint; problem drinker; prospective; receptor; research study; secondary endpoint; standard of care; targeted treatment; therapeutic development; therapeutically effective; translational study; treatment arm

Abstract Alcoholic (AH) is a leading cause of liver-related morbidity and mortality with a remarkable paucity of effective therapeutics. This application represents a coordinated submission of several NIAAA-funded consortia which have come together as the Alcoholic Hepatitis Network (AlcHepNet) to better understand AH and develop novel effective and safe therapy for severe AH. The overarching aims of this consortium are to: (1) perform studies to better understand the pathogenesis and main determinants of outcome, particularly in severe AH, (2) identify novel targets for therapy of AH, and (3) perform phase 2B studies of compounds that are already available and can be repurposed as safe and effective therapy for severe AH. Under the umbrella of these larger aims, the aims of this proposal are: 1. To conduct a prospective, multicenter, observational study of patients with AH and suitable controls that serves as the foundation for conducting novel mechanistic and therapeutic studies. We will consolidate and extend our longitudinal database of (1) clinical and laboratory information and (2) a bio-sample repository from subjects with AH of varying severity and matched-controls. This database will: (a) provide unique information on the outcomes and pathobiology of AH, (b) support translational research designed to identify novel targets for treatment, and (c) be used to generate systems biology based informatics-integrated databases that will serve as a resource for all researchers interested in AH. 2. To perform a multicenter prospective, randomized phase 2B clinical trial of G-CSF and Anakinra versus standard medical therapy with Prednisolone in patients with severe AH. This aim will test the hypothesis that both active treatment arms with G-CSF and the IL-1 receptor antagonist Anakinra are superior to the stardard of care (i.e. prednisolone) in patients with severe AH. The choice of these agents is based on: (1) literature demonstrating a role for inflammation and inflammasome activation in severe AH, (2) several pilot studies demonstrating therapeutic benefit with G-CSF, (3) interim analysis of an ongoing trial suggesting a mortality benefit with Anakinra in patients with AH. This phase 2B efficacy trial will be conducted across nine clinical centers and coordinated by a Data Coordinating Center (DCC). The primary endpoint will be mortality at day 90. The investigators and the AlcHepNet is uniquely positioned to perform the proposed study given substantial breadth and depth of expertise related to AH, clinical trial conduct, and therapeutic development. By testing promising therapies for AH and concurrently collecting well annotated patient samples and datasets, this proposal will have a strong and lasting impact on the field.

抽象的 酒精（AH）是与肝有关的发病率和死亡率的主要原因 缺乏有效的治疗剂。该申请代表协调的提交 几个NIAAA资助的财团已作为酒精性肝炎网络融合在一起 （Alchepnet）更好地理解AH并开发出新颖的有效且安全的治疗 啊。该财团的总体目的是：（1）进行研究以更好地理解 结局的发病机理和主要决定因素，特别是在严重AH中，（2）确定 AH治疗的新靶标，（3）对化合物进行2B期研究 已经可用，可以重新使用为严重AH的安全有效疗法。在 这些较大目标的保护伞，该提案的目的是：1。 对患有AH的患者和适当对照组的多中心，观察性研究 进行新的机械和治疗研究的基础。我们将 合并并扩展我们的纵向数据库（1）临床和实验室信息以及 （2）来自具有不同严重性和匹配控制的受试者的生物样本存储库。 该数据库将：（a）提供有关AH的结果和病理学的独特信息，（b） 支持旨在确定治疗新目标的翻译研究，并使用（c） 生成基于系统生物学的信息学集成数据库，这些数据库将作为一个 所有对AH感兴趣的研究人员的资源。 2。要执行多中心前瞻性， G-CSF和Anakinra与标准医学的随机2B随机2B临床试验 严重AH患者的泼尼松龙治疗。这个目标将检验以下假设 G-CSF和IL-1受体拮抗剂Anakinra的主动治疗臂都是优越的 患有严重AH患者的护理标明（即泼尼松龙）。这些代理商的选择 基于：（1）文献证明了在炎症和炎症中的作用 严重的AH，（2）一些试验研究，证明了G-CSF治疗益处，（3）临时 对正在进行的试验的分析表明，ANAKINRA对AH患者的死亡率受益。 该阶段2b疗效试验将在9个临床中心进行，并通过 数据协调中心（DCC）。主要终点将是第90天的死亡率。 研究人员和炼金术机构是独特的定位，可以进行拟议的研究 与AH，临床试验和治疗性有关的专业知识的大量广度和深度 发展。通过测试AH的有希望疗法并同时收集注释良好 患者样品和数据集，该提案将对该领域产生强烈而持久的影响。