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The Saint Louis University Component of the NASH CRN

NASH CRN 的圣路易斯大学组成部分

基本信息

批准号：
10666704
负责人：
BRENT A NEUSCHWANDER-TETRI
金额：
$ 58.15万
依托单位：
SAINT LOUIS UNIVERSITY
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：
2002-05-20 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10666704
关键词：
Address Adult Affect Bacteria Bioinformatics Biological Markers Blood Butter Butyric Acids Cancer Etiology Cardiovascular system Cell Line Cell physiology Cessation of life Child Childhood Cirrhosis Clinical Clinical Course of Disease Clinical Management Clinical Research Clinical Trials Collaborations Colon Cost Analysis Cost of Illness Data Data Coordinating Center Databases Development Diagnosis Diagnostic tests Dietary Fiber Disease Disease Progression Energy-Generating Resources Enrollment Evidence based treatment Feasibility Studies Funding Gastrointestinal tract structure Genetic Health Health Care Costs Hepatocellular Damage Histologic Image Incidence Inflammation Inflammatory Intestinal permeability Knowledge Laboratory Study Link Liver Liver diseases Longitudinal cohort Losartan Malignant Neoplasms Malignant neoplasm of liver Metabolic Metabolism Methods Mission Modeling National Institute of Diabetes and Digestive and Kidney Diseases Natural History North America Outcome Pathogenesis Patients Persons Pharmaceutical Preparations Phase Phenotype Pilot Projects Population Study Positioning Attribute Prevention Prevention strategy Preventive measure Primary Malignant Neoplasm of Liver Prodrugs Proteomics Public Health Randomized Research Research Personnel Risk Risk Factors Site Techniques Therapeutic Agents Therapeutic Trials Translating Translational Research United States United States National Institutes of Health Universities Validation adverse outcome animal data biomarker discovery biomarker validation clinical application clinical center clinical material clinical practice cohort cost cost effective diabetogenic dietary supplements disease natural history elastography follow-up gut microbiome human data improved innovation lipidomics liver injury liver transplantation longitudinal database meetings metabolomics microbiome mortality non-alcoholic non-alcoholic fatty liver disease nonalcoholic steatohepatitis novel therapeutics phase III trial prevent prognostication prospective public-private partnership translational study treatment response treatment strategy treatment trial tributyrin

项目摘要

Abstract This application is for the Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) clinical center at Saint Louis University and its pediatric component at Baylor University. The NASH Clinical Research Network (NASH CRN) has been sponsored by the NIDDK since 2002 with renewals in 2009 and 2014. Nonalcoholic fatty liver disease (NAFLD) affects more than one out of three adults and one out of five children the U.S. NAFLD, and especially its most severe subset nonalcoholic steatohepatitis (NASH), may lead to cirrhosis and primary liver cancer resulting in death or liver transplant and substantial health burdens and costs. The NASH CRN is ideally and uniquely positioned to impact the growing public health significance of NASH that can only be addressed via a large research consortium. The primary objective of the NASH CRN is to perform clinical trials of therapeutic agents for NASH and NAFLD in adults and children. A closely linked and high priority secondary 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, prevention, treatment, and clinical management. In the next phase of the NASH CRN, the adult and pediatric therapeutic trials initiated during the previous funding cycles 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, cost-effective and broadly applicable. The longitudinal cohort of adults and children with NAFLD collected over the past decade will be extended to prospectively define the natural history of the disease, the cardiovascular and metabolic risk factors, and will aid in biomarker discovery and validation. This cohort will also facilitate the development and validation of non-invasive techniques to identify those with NASH, predict who will respond to treatments, and identify factors affecting disease progression. The treatment trial proposed in this application is a phase 2a trial of a dietary supplement called tributyrin. Tributyrin makes up about 3% of butter and is a prodrug of butyric acid. Butyric acid is an important metabolite produced by bacteria in the GI tract during their normal metabolism of dietary fiber. Butyric acid has been shown to be the primary energy source for the layer of cells that line the colon where it promotes the function of these cells and prevents harmful bacterial products from entering the blood and damaging the liver. It has also been found to have beneficial effects on metabolism throughout the body. Animal data supports the rationale for studying butyric acid, or its precursor tributyrin, in treating NASH but human data are very limited. Additional translational studies are proposed in this application to mechanistically understand the benefits of tributyrin treatment gut permeability and whole-body metabolism. The NASH CRN is poised to continue its major impact on the field and directly advance the mission of the National Institutes of Health to improve the health of the public.

摘要

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Magnetic resonance elastography biomarkers for detection of histologic alterations in nonalcoholic fatty liver disease in the absence of fibrosis.

DOI：
10.1007/s00330-021-07988-6
发表时间：
2021-11
期刊：
European radiology
影响因子：
5.9
作者：
Qu Y;Middleton MS;Loomba R;Glaser KJ;Chen J;Hooker JC;Wolfson T;Covarrubias Y;Valasek MA;Fowler KJ;Zhang YN;Sy E;Gamst AC;Wang K;Mamidipalli A;Schwimmer JB;Song B;Reeder SB;Yin M;Ehman RL;Sirlin CB
通讯作者：
Sirlin CB

An evolving scientific basis for the prevention and treatment of pediatric obesity.

DOI：
10.1038/ijo.2014.49
发表时间：
2014-07
期刊：
INTERNATIONAL JOURNAL OF OBESITY
影响因子：
4.9
作者：
Katzmarzyk, P. T.;Barlow, S.;Bouchard, C.;Catalano, P. M.;Hsia, D. S.;Inge, T. H.;Lovelady, C.;Raynor, H.;Redman, L. M.;Staiano, A. E.;Spruijt-Metz, D.;Symonds, M. E.;Vickers, M.;Wilfley, D.;Yanovski, J. A.
通讯作者：
Yanovski, J. A.

Gut Microbiota to Microglia: Microbiome Influences Neurodevelopment in the CNS.

肠道菌群至小胶质细胞：微生物组影响中枢神经系统的神经发育。