Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

非酒精性脂肪性肝炎临床研究网络 (NASH CRN)

• 批准号: 10240598
• 负责人: NORAH A. TERRAULT
• 金额: $ 15.13万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240598
• 关键词: Address; Adolescent; Adult; Affect; Amlodipine; Ancillary Study; Archives; Autophagocytosis; Biological Markers; Cardiovascular Diseases; Cardiovascular system; Child; Childhood; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Collaborations; Complementary DNA; Coupled; DNA; Data; Data Coordinating Center; Databases; Diabetes Mellitus; Diagnosis; Disease; Disease Marker; Disease Progression; Double-Blind Method; Eating; Economic Burden; Enrollment; Epidemiology; Extrahepatic; Fatty Liver; Funding; Genetic; Goals; Health; Hepatic; High Prevalence; Human; Immunologics; Immunology; Incidence; Individual; Knowledge; Laboratory Study; Length; Life; Link; Lipids; Liver; Liver diseases; Longitudinal cohort; Longitudinal cohort study; Losartan; Malignant Neoplasms; Malignant neoplasm of liver; Measurement; Measures; Metabolic; Metabolic syndrome; Methods; Modeling; Modification; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; North America; Obesity; Outcome; Participant; Pathogenesis; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Placebos; Plasma; Population; Population Study; Positioning Attribute; Prevalence; Prevention; Prevention strategy; Primary carcinoma of the liver cells; Prospective cohort; Publications; Randomized; Research; Resources; Risk; Risk Factors; Role; Safety; Sampling; Serum; Severity of illness; Stains; Testing; Therapeutic; Therapeutic Studies; Therapeutic Trials; Time; Tissues; Translational Research; United States; adverse outcome; base; biobank; biological specimen archives; burden of illness; chronic liver disease; clinical application; clinical center; clinical material; clinical research site; cohort; comorbidity; disease natural history; efficacy outcomes; experience; follow-up; liver biopsy; microbiome; mortality; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; novel marker; novel therapeutics; patient subsets; pediatric non-alcoholic fatty liver disease; pediatric patients; phase 2 study; prospective; recruit; success; tool; translational study; treatment strategy

Project Summary Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) ranks as one of the most important causes of chronic liver disease in the United States, with 1 of every 3 adults and 1 of every 5 children affected. NAFLD, especially NASH, is associated with increased liver, cardiovascular and cancer-related mortality. The NASH Clinical Research Network (NASH CRN) was established in 2002 to conduct research related to its clinical features, risk factors, pathogenesis, natural history and treatment in children and adults. Over the last funding cycle, the CRN has accrued a comprehensive database of 4,544 patients from five studies during the current funding period (to 1 Oct 18). Two clinical trials were completed (FLINT and CyNCh) and The Losartan for Pediatric NAFLD (STOP-NAFLD) trial is underway with first patient randomized in Oct 2018. Additionally, the NASH CRN has archived a total of 504,685 biospecimens (serum, plasma, liver tissue, DNA ad cDNA) in the NIDDK Biorepository, and 28,436 samples have been withdrawn for translational research using the Ancillary Studies mechanism. Since 2004, a total of 31 publications have resulted from the 104 approved Ancillary Studies. Building on the success of the last funding cycle, the NIDDK has issued RFA- DK-08-505 with the objectives of continue the NASH CRN for an additional 5 years. The objectives of the NASH CRN during this next funding period are: (a) to complete the network-wide studies initiated during the last funding period. These are two observational longitudinal cohort studies (the Adult and Pediatric NAFLD Database 2 studies) and a randomized double blind controlled therapeutic trial of losartan for NAFLD in children (STOP-CO, n=110). The NAFLD database may be amended to meet additional outcome goals during the next funding period. These modifications may include extending the length of follow-up of those enrolled, consideration of a follow-up liver biopsy in a subset of patients, and expansion to include greater focus on cardiovascular, diabetes and cancer-related outcomes; (b) to conduct new translational studies based on the clinical material and archived biospecimens from previous funding periods including novel markers of autophagy, an important means of controlling cellular lipids that is understudied relative to other lipid-regulating pathways in the liver and potential role in NAFLD disease severity; and (c) to conduct additional novel therapeutic studies in adults and children with NASH, such as the proposed phase 2 study of amlodipine, as pro-autophagic therapy, in children and adults with NASH (AMPAT Trial). Ancillary studies will leverage new collaborations (e.g. immunology, microbiome) to develop a comprehensive model of NAFLD/NASH which will allow identification of adults and children at risk and establish effective preventive and treatment strategies against NASH.

项目概要 非酒精性脂肪肝（NAFLD）和非酒精性脂肪性肝炎（NASH）被列为最常见的疾病之一。 在美国，每 3 名成人中就有 1 名患者患有慢性肝病，每 5 名儿童中就有 1 名患者患有慢性肝病 做作的。 NAFLD，尤其是 NASH，与肝脏、心血管和癌症相关的增加有关 死亡。 NASH临床研究网络（NASH CRN）成立于2002年，开展研究 与儿童和成人的临床特征、危险因素、发病机制、自然史和治疗有关。 在上一个资助周期中，CRN 积累了一个包含来自五个国家的 4,544 名患者的综合数据库。 当前资助期间（截至2018年10月1日）的研究。完成两项临床试验（FLINT和CyNCh） 氯沙坦治疗儿科 NAFLD (STOP-NAFLD) 试验正在进行中，第一位患者于 10 月随机分组 2018 年。此外，NASH CRN 已归档了总共 504,685 个生物样本（血清、血浆、肝组织、 DNA 和 cDNA）在 NIDDK 生物储存库中，并已提取 28,436 个样本进行翻译 使用辅助研究机制进行研究。自2004年以来，共发表了31篇论文 104 项批准的辅助研究。基于上一个融资周期的成功，NIDDK 发布了 RFA- DK-08-505 的目标是继续 NASH CRN 5 年。该计划的目标 NASH CRN 在下一个资助期内是： (a) 完成上一个资助期间发起的全网络研究。这是两个观察 纵向队列研究（成人和儿童 NAFLD 数据库 2 研究）和随机双盲 氯沙坦治疗儿童 NAFLD 的对照治疗试验（STOP-CO，n=110）。 NAFLD 数据库可能是 进行修改，以实现下一个资助期间的额外成果目标。这些修改可能包括 延长入组患者的随访时间，考虑对一部分患者进行随访肝活检 患者，并扩展到更加关注心血管、糖尿病和癌症相关结果； (b) 根据临床材料和存档的生物样本进行新的转化研究 之前的资助期包括自噬的新标记物，自噬是控制细胞脂质的重要手段 相对于肝脏中的其他脂质调节途径以及 NAFLD 疾病中的潜在作用，这一点尚未得到充分研究 严重程度；和 (c) 对患有 NASH 的成人和儿童进行其他新的治疗研究，例如拟议的 氨氯地平作为促自噬疗法治疗儿童和成人 NASH 的 2 期研究（AMPAT 试验）。 辅助研究将利用新的合作（例如免疫学、微生物组）来开发全面的 NAFLD/NASH 模型将允许识别处于危险中的成人和儿童并建立有效的 NASH 的预防和治疗策略。