Non Alcoholic Steatohepatitis Clinical Research Network

描述(由申请人提供)：本申请是非酒精性脂肪性肝炎临床研究网络(NASH CRN)的病例西部储备大学(CWRU)临床站点及其子站点的延续。非酒精性脂肪性肝病(NAFLD)在北美影响着近三分之一的成年人和五分之一的儿童，在美国是一个主要的公共卫生问题。非酒精性脂肪肝，特别是非酒精性脂肪性肝炎(NASH)，会导致终末期肝病和原发性肝癌，以及与肝脏、心血管和癌症相关的死亡，导致医疗负担和成本的大幅增加。NASH CRN是影响NASH日益增长的公共卫生负担的理想和独特的定位，只有通过这个在以前的周期中有成功记录的大型研究联盟才能解决这一问题。NASH CRN的主要目标是在成人和儿童中进行NASH和NAFLD的临床研究。另一个高度优先的目标是在NASH和NAFLD中进行转译研究，重点研究发病机制，为了解自然病史和开发更好的诊断、治疗和临床管理方法提供基础。在NASH CRN的下一阶段，在前一个供资周期启动的成人和儿童治疗试验将是 将启动新的治疗试验，包括2a阶段机制证明和2b阶段临床试验，以开发安全、有效、简单和廉价的循证治疗方案。成人和儿童NAFLD患者的纵向队列将扩大，这将前瞻性地定义疾病的自然病史、心血管和代谢风险因素，并将有助于生物标记物的发现和验证，以及非侵入性技术的开发和验证，以评估和识别NASH/NAFLD患者、谁将做出反应以及疾病进展有多快。自NASH CRN成立以来，CWRU在NASH CRN的临床和翻译研究成功方面发挥了主导作用。在皮文斯和弗林特试验中，CWRU都是领先的招生地点。CWRU的研究人员在提高对NAFLD包括心血管和骨骼肌功能障碍在内的全身异常的了解方面具有独特的地位。骨质疏松症和转化生长因子�超家族成员肌肉抑制素作为NASH的治疗靶点的作用是一种针对这种几乎无处不在的疾病的新靶点的范式转换方法。鉴于来自CWRU的高招聘、高质量的数据，以及我们对合作成功的持续承诺，NASH CRN准备继续其在该领域的主要影响，并直接推动NIH改善公众健康的使命。

DESCRIPTION (provided by applicant): This application is for the Continuation of the Case Western Reserve University (CWRU) Clinical Site and its Subsites of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Nonalcoholic fatty liver disease (NAFLD) affects nearly a third of adults and a fifth of children in North America and is a major public health issue in the United States. NAFLD, and especially nonalcoholic steatohepatitis (NASH), lead to end-stage liver disease and primary liver cancer, as well as liver-, cardiovascular-, and cancer-related mortality, resulting in major increases in health burdens and costs. The NASH CRN is ideally and uniquely positioned to impact the growing public health burden of NASH that can only be addressed through this large research consortium with a demonstrated track record of success in previous cycles. The primary objective of the NASH CRN is to perform clinical research on NASH and NAFLD in adults and children. Another high priority objective is to conduct translational research in NASH and NAFLD focusing on the pathogenesis that will provide the basis for understanding the natural history and developing means of better diagnosis, treatment, and clinical management. In the next phase of the NASH CRN, the adult and pediatric therapeutic trials initiated during the previous funding cycle will be completed, and new therapeutic trials, including phase 2a proof of mechanism and phase 2b clinical trials will be initiated, to develop evidence-based treatment options that are safe, effective, simple, and inexpensive. The longitudinal cohort of adults and children with NAFLD will be extended, which will prospectively define the natural history of the disease, the cardiovascular and metabolic risk factors, and will aid in biomarker discovery and validation, and development and validation of non-invasive techniques to evaluate and identify those with NASH/NAFLD, who will respond, and how quickly the disease is progressing. CWRU has played a leading role in both the clinical and translational research success of the NASH CRN since the inception. CWRU was a leading enrolling site in both the PIVENS and FLINT trials. CWRU investigators are uniquely placed in improving understanding of systemic abnormalities including cardiovascular and skeletal muscle dysfunction in NAFLD. The role of sarcopenia and myostatin, a TGF� superfamily member, as a therapeutic target in NASH is a paradigm shifting approach to novel targets for the nearly ubiquitous disease. Given the high recruitment, retention and quality of data from CWRU, and our continued commitment to the success of the collaboration, the NASH CRN is poised to continue its major impact on the field and directly advance the mission of the NIH to improve the health of the public.