Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

非酒精性脂肪性肝炎临床研究网络 (NASH CRN)

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要非酒精性脂肪肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）排名最多美国慢性肝病的重要原因，每3名成年人中有1个，每5个孩子中有1个做作的。 NAFLD，尤其是NASH，与肝脏，心血管和癌症有关死亡。 NASH临床研究网络（NASH CRN）于2002年成立与儿童和成人的临床特征，危险因素，发病机理，自然病史和治疗有关。在上一个融资周期中，CRN累积了4,544名患者的综合数据库在当前资金期间（至10月18日）的研究。完成了两个临床试验（Flint和Cynch）小儿NAFLD（Stop-NaFLD）试验的Losartan正在进行中，第一位患者在OCT中随机进行 2018年。此外，NASH CRN总共存档了504,685个生物测量（血清，血浆，肝组织， NIDDK生物座的DNA AD cDNA），已撤回了28,436个样品以进行翻译使用辅助研究机制的研究。自2004年以来，总共有31个出版物由 104批准的辅助研究。 NIDDK以最后的融资周期的成功为基础，发行了RFA- DK-08-505的目标是继续使用Nash CRN 5年。目标的目标在此下一个资金期间，纳什CRN是：（a）完成在最后一个资金期间开始的网络范围内的研究。这是两个观察纵向队列研究（成人和小儿NAFLD数据库2研究）和随机双盲 Losartan在儿童中为NAFLD的控制治疗试验（停止CO，n = 110）。 NAFLD数据库可能是修订以实现下一个资金期间的额外结果目标。这些修改可能包括延长了入学者的随访时间，考虑了一部分的随访肝活检患者，并扩展将更加关注心血管，糖尿病和与癌症相关的结局；（b）根据临床材料和存档的生物测量进行新的翻译研究以前的融资期，包括自噬的新标记，这是控制细胞脂质的重要手段相对于肝脏中其他脂质调节途径的研究及其在NAFLD疾病中的潜在作用。严重程度；和（c）在成人和纳什儿童中进行其他新的治疗研究，例如提议在患有NASH的儿童和成人中，氨氯地平的2阶段研究（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 NAFLD/NASH的模型，该模型将允许识别有风险的成年人和儿童并建立有效预防和治疗策略针对纳什。