Non Alcoholic Steatohepatitis Clinical Research Network

描述（由申请人提供）：本申请用于延续凯斯西储大学（CWRU）临床研究中心及其非酒精性脂肪性肝炎临床研究网络（NASH CRN）的子研究中心。非酒精性脂肪肝（NAFLD）影响北美近三分之一的成年人和五分之一的儿童，是美国的一个主要公共卫生问题。NAFLD，特别是非酒精性脂肪性肝炎（NASH），导致终末期肝病和原发性肝癌，以及肝脏，心血管和癌症相关的死亡率，导致健康负担和成本的大幅增加。NASH CRN具有理想和独特的定位，可以影响NASH日益增长的公共卫生负担，这只能通过这个大型研究联盟来解决，该联盟在以前的周期中具有成功的记录。NASH CRN的主要目的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中进行转化研究，重点是发病机制，这将为理解自然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，在上一个资助周期中启动的成人和儿童治疗试验将 已完成，并将启动新的治疗试验，包括2a期机制验证和2b期临床试验，以开发安全、有效、简单和廉价的循证治疗方案。NAFLD成人和儿童的纵向队列将得到扩展，这将前瞻性地定义疾病的自然史，心血管和代谢风险因素，并将有助于生物标志物的发现和验证，以及非侵入性技术的开发和验证，以评估和识别NASH/NAFLD患者，谁将响应，以及疾病进展的速度。自成立以来，CWRU在NASH CRN的临床和转化研究成功方面发挥了主导作用。CWRU是PIVENS和FLINT试验的主要招募中心。CWRU研究人员在提高对NAFLD中包括心血管和骨骼肌功能障碍在内的全身异常的理解方面处于独特的地位。肌减少症和肌生长抑制素（TGF β超家族成员）作为NASH治疗靶点的作用是一种范式转变方法，可用于治疗几乎无处不在的疾病。鉴于CWRU的高招募，保留和数据质量，以及我们对合作成功的持续承诺，NASH CRN准备继续对该领域产生重大影响，并直接推进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.