Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

如果没有共同努力，非酒精性脂肪性肝炎（NASH）的流行就不会得到遏制。 识别、预防和治疗驱动人类 NASH 发病机制和进展的因素。致地址 为了应对这一挑战，NIDDK 建立了 NASH 临床研究网络 (NASH CRN)，这是一个致力于 推进与成人和儿童 NASH 相关的临床和转化科学。 CRN 广泛 被认为是 NASH 领域的领导者，因为它开发了世界上最大、特性最好的、 对成人和儿童 NASH 患者进行了最长的前瞻性随访，并进行了多项明确的研究 NASH 受试者的前瞻性随机安慰剂对照试验 (RCT)。展望未来，CRN 将 利用这项工作产生的信息来推进诊断测试和疾病生物标志物的开发 NASH 的进展和安全、具有成本效益的治疗方法。此竞争性续订申请来自 杜克/卢里儿童医院网站详细介绍了我们网站接下来将完成的工作计划 作为 CRN 成员的资金周期。除了我们确保所有 CRN 活动成功的详细方法之外 （目标 1），我们进一步提出了一项新的多中心随机对照试验，评估阿托伐他汀作为仿制药的“再利用”药物 NASH 的治疗（目标 2）和相关转化科学提供有关如何治疗的机制信息 他汀类药物影响 NASH（目标 3）。后两个项目是我们早期 CRN 研究的自然延伸 证明了 Hedgehog（一种脂质调节信号通路）在确定疾病进展中的重要性 NASH 和 NASH 相关纤维化。这些目标的实现将进一步推进 NASH CRN 任务 描述 NASH 自然史并确定安全且经济有效地预防和治疗的新颖干预措施 治疗 NASH。

The epidemic of nonalcoholic steatohepatitis (NASH) will not be constrained without collaborative efforts to identify, prevent, and treat the factors that drive NASH pathogenesis and progression in humans. To address this challenge the NIDDK established the NASH Clinical Research Network (NASH CRN), a consortium devoted to advancing clinical and translational science pertinent to adult and pediatric NASH. The CRN is widely considered to be a leader in the NASH field because it has developed the world’s largest, best-characterized, and longest prospectively-followed cohort of adult and pediatric NASH patients and done several definitive prospective randomized placebo-controlled trials (RCTs) in NASH subjects. Moving forward, the CRN will leverage information generated by this work to advance development of diagnostic tests, biomarkers of disease progression, and safe, cost-effective treatments for NASH. This competitive renewal application from the Duke/Lurie Children’s Hospital site details our site’s plans for the work that we will accomplish during the next funding cycle as CRN members. In addition to our detailed approach to ensure success of all CRN activities (Aim 1), we further propose a new multi-center RCT evaluating atorvastatin as a generic “repurposed” drug for the treatment of NASH (Aim 2) and related translational science to provide mechanistic information about how statins impact NASH (Aim 3). The latter two projects are natural extensions of our earlier CRN studies which demonstrated the importance of Hedgehog, a lipid-regulated signaling pathway, in determining progression of NASH and NASH-related fibrosis. Accomplishment of these Aims will advance NASH CRN missions by further delineating NASH natural history and identifying novel interventions that safely and cost-effectively prevent and treat NASH.