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：
9323378
负责人：
NORAH A. TERRAULT
金额：
$ 34.96万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9323378
关键词：
Address Adolescent Adult Affect Biological Markers Cardiovascular system Child Childhood Clinical Clinical Course of Disease Clinical Management Clinical Research Clinical Trials Collaborations Cysteamine Data Data Coordinating Center Databases Development Diabetes Mellitus Diagnosis Diagnostic Disease Progression Disease model Double-Blind Method Enrollment Fatty Liver Feasibility Studies Funding Future Genetic Goals Histologic Image Incidence Knowledge Laboratory Study Length Link Liver Liver diseases Longitudinal cohort study Malignant Neoplasms Methods Mission Modeling Modification Morbidity - disease rate National Institute of Diabetes and Digestive and Kidney Diseases Natural History North America Outcome Pathogenesis Patient risk Patients Phase Phenotype Pilot Projects Population Population Study Positioning Attribute Prevention strategy Proteomics Public Health Randomized Research Risk Risk Factors Risk stratification Sampling Therapeutic Therapeutic Studies Therapeutic Trials Translating Translational Research United States United States National Institutes of Health Work adverse outcome base chronic liver disease clinical application clinical imaging clinical material clinical practice cohort diabetogenic effective therapy follow-up improved innovation liver biopsy longitudinal database meetings metabolomics mortality non-alcoholic fatty liver nonalcoholic steatohepatitis novel therapeutics patient subsets prognostic public-private partnership sobriety translational study treatment response treatment strategy

项目摘要

DESCRIPTION (provided by applicant): 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 treatmen in children and adults. Over the last funding cycle, the CRN has enrolled 3,021 patients (as of September, 2013) into a combination of two clinical trials (FLINT and CyNCh) and a longitudinal NAFLD patient database. Encouraged by the advances made by the CRN, 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 successfully complete the 3 network-wide studies initiated during the last funding period. These are an observational longitudinal cohort study of NAFLD in adults and children (NAFLD Database 2 study, n=1,874), a randomized double blind controlled therapeutic trial of INT-747 for NASH (FLINT, n=283) and a randomized controlled therapeutic trial of cysteamine for NAFLD in children (CYNCH, n=160). 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, expansion to include cardiovascular and diabetes-related outcomes, and enrollment of carefully selected controls without NAFLD; (b) to successfully complete a large number of ancillary and pilot/feasibility studies that were approved and initiated by the NASH CRN during the current funding; (c) to conduct additional novel therapeutic studies in adults and children with NASH, including phase 2a proof of mechanism trials and phase 2b clinical trials. Additional public-private partnerships will be established to perform these trials; (d) to conduct new translational studies based on the clinical material, imaging/elastometry and biospecimens (300,000+) collected during previous funding periods of the NASH CRN. These studies will leverage collaborations with groups with specific expertise (e.g. genetics, lipidomics, metabolomics) to develop a comprehensive model of NAFLD/NASH which will allow identification of adults and children at risk, stratification of risk of liver and non-liver morbidity and mortality, and establishment of effective preventive and treatment strategies against NASH. This large and highly characterized cohort, together with the NASH CRN expertise in leveraging public-private partnerships to perform innovative therapeutic trials, is uniquely positioned to address these important clinical needs. In meeting those needs, the NASH CRN will have a major impact on the field and directly advance the mission of the National Institutes of Health to improve the health of the public.

描述（由申请人提供）：非酒精性脂肪肝疾病（NAFLD）和非酒精性脂肪性肝炎（NASH）是美国慢性肝病最重要的原因之一，每3名成年人中有1个，每5名儿童中有1个受影响。 NAFLD，尤其是NASH，与肝脏，心血管和与癌症相关的死亡率增加有关。 NASH临床研究网络（NASH CRN）于2002年成立，旨在进行与其临床特征，危险因素，发病机理，自然病史和儿童和成人治疗有关的研究。在上一个融资周期中，CRN已将3,021名患者（截至2013年9月）招募，组合了两个临床试验（Flint和Cynch）和一个纵向NAFLD患者数据库的组合。在CRN的进步的鼓励下，NIDDK已发行了RFA-DK-08-505，其目标是继续使用Nash CRN 5年。在下一个资金期间，NASH CRN的目标是：（a）成功完成在上一个资金期间启动的3个网络范围的研究。这些是成人和儿童NAFLD的观察纵向队列研究（NAFLD数据库2研究，n = 1,874），一项INT-747的随机双盲盲型治疗试验（NASH，FLINT，n = 283）和NAFLECTICATICATIC在儿童中的NAFLECTIMATIC试验（flint，n = 283）和儿童中Nafld的司法性试验（Cynch）（Cynch），N = 160。可以对NAFLD数据库进行修改，以实现下一个资金期间的其他结果目标。这些修改可能包括延长参与者的随访时间，一部分患者的随访活检的考虑，包括心血管和糖尿病相关结果的扩张以及没有NAFLD的精心选择的对照；（b）成功完成大量辅助和试点/可行性研究，这些研究在当前资金期间得到了纳什CRN的批准和启动；（c）在成年人和NASH儿童中进行其他新的治疗研究，包括2A阶段的机制试验证明和2B期临床试验。将建立其他公私合作伙伴关系来执行这些试验；（d）在纳什CRN的先前资金期间收集的基于临床材料，成像/弹性测定法（300,000）（300,000+）进行新的翻译研究。这些研究将利用具有特定专业知识（例如遗传学，脂质组学，代谢组学）的团体的合作来开发NAFLD/NASH的全面模型，这将允许鉴定有风险的成年人和儿童，肝脏风险分层，非肝病发病率和死亡率，以及建立有效的预防性预防和治疗策略。这种大型且具有高度特征的队列，以及Nash CRN在利用公私合作伙伴关系来进行创新治疗试验方面的专业知识，在满足这些重要的临床需求方面具有独特的位置。在满足这些需求时，纳什CRN将对该领域产生重大影响，并直接推动美国国立卫生研究院的使命，以改善公众的健康。