Nonalcoholic Steatohepatitis Clinical Research Network

非酒精性脂肪性肝炎临床研究网络

• 批准号: 8012896
• 负责人: ARUN J SANYAL
• 金额: $ 10.48万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8012896
• 关键词: Adult; Ancillary Study; Antioxidants; Arts; Attention; Biological Markers; Body mass index; Cardiovascular system; Child; Chronic; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Collection; Control Groups; Data; Databases; Development; Diabetes Mellitus; Diagnostic; Disease Progression; Double-Blind Method; Eicosanoids; Enrollment; Fatty Acids; Fatty Liver; Feasibility Studies; Funding; Gastroplasty; Generations; Genetic; Goals; Guidelines; Health; Histology; Incidence; Individual; Inflammatory; Insulin Resistance; Length; Lipids; Liver; Liver diseases; Longitudinal Studies; Mass Spectrum Analysis; Medical; Metabolic; Metabolic Pathway; Metformin; Methods; Modification; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Outcome; Pathogenesis; Patients; Pattern; Phenotype; Pioglitazone; Placebos; Polyunsaturated Fatty Acids; Principal Investigator; Procedures; Process; Production; Proteomics; Publications; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Reporting; Research; Risk; Risk Factors; Sampling; Serum; Specificity; Steatohepatitis; Systems Biology; Testing; Therapeutic; Therapeutic Studies; Therapy Clinical Trials; Tissue Sample; United States; United States National Institutes of Health; Vitamin E; base; clinical material; control trial; disease natural history; effective therapy; fatty acid metabolism; follow-up; improved; innovation; insight; insulin sensitizing drugs; lipid biosynthesis; liver biopsy; meetings; metabolomics; minimally invasive; non-alcoholic fatty liver; non-diabetic; nonalcoholic steatohepatitis; novel; operation; oxidized lipid; prospective; public health relevance; success

DESCRIPTION (provided by applicant): Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in the United States. It encompasses both a fatty liver and nonalcoholic steatohepatitis (NASH). The NASH Clinical Research Network (NASH CRN) was established in 2002 to conduct research related to the clinical features, risk factors, pathogenesis, natural history and treatment of NAFLD in children and adults. Encouraged by its success, the NIDDK has issued RFA-DK-08-505 whose objective is to continue the NASH CRN for five more years. The objectives of the NASH CRN during the next five years are: (1) to successfully complete three network wide studies initiated during the initial funding period. These include an observational longitudinal study of NAFLD in adults and children (NAFLD database study, n=1215), a randomized double blind controlled trial of pioglitazone or vitamin E vs. placebo (PIVENS) (n=247) in nondiabetic adults with NASH, and a randomized double blind controlled trial of metformin or vitamin E vs. placebo (TONIC) (n= 173). These studies are fully enrolled. The NAFLD database will be amended to allow further follow up of enrolled subjects, perform liver biopsies on selected subjects and add carefully defined controls as well as additional subjects with NAFLD. The rationale for this is to definitively evaluate the natural history of the disease, develop and validate biomarkers and complete ancillary studies that are still underpowered despite use of the current database, (2) to complete the numerous pilot and ancillary studies that have been initiated, (3) to perform additional therapeutic trials in adults and children with NASH. The specific studies will be based on proposals received from individual centers that are approved by the NASH CRN steering committee and the NIDDK for which funding is available, and (4) to conduct new ancillary studies proposed by individual centers. Two studies are proposed by this center: (a) to validate the metabolomic signature of NASH. Preliminary studies have identified a distinct lipidomic signature of NASH, (b) to perform a randomized controlled trial of laparoscopic adjustable band gastroplasty (LABG) for adults with NASH who have a BMI between 30-45. This trial will test the hypothesis that LABG is a safe and effective treatment of NASH. Together, all of these studies are directly aligned with the NIH liver action plan for NAFLD. Public Health Relevance: (provided by the applicant): NAFLD and NASH are important health problems and their incidence is expected to increase. During the initial funding period, the CRN has made important contributions to the field of NAFLD and NASH, however there remain numerous unanswered questions. During the next funding period, the CRN will continue to investigate risk factors, clinical aspects, natural history and optimal treatment for NASH and associated conditions

描述（由申请人提供）： 非酒精性脂肪肝（NAFLD）是美国慢性肝病的常见原因。它包括脂肪肝和非酒精性脂肪性肝炎（NASH）。NASH临床研究网络（NASH CRN）成立于2002年，旨在开展与儿童和成人NAFLD的临床特征、危险因素、发病机制、自然史和治疗相关的研究。受到成功的鼓舞，NIDDK发布了RFA-DK-08-505，其目标是将NASH CRN再延续五年。NASH CRN在未来五年的目标是：（1）成功完成在初始资助期间启动的三项网络范围的研究。其中包括一项成人和儿童NAFLD观察性纵向研究（NAFLD数据库研究，n=1215），一项在非糖尿病成人NASH患者中进行的吡格列酮或维生素E与安慰剂（PIVENS）（n=247）的随机双盲对照试验，以及一项二甲双胍或维生素E与安慰剂（TONIC）（n= 173）的随机双盲对照试验。这些研究已全部入组。将修订NAFLD数据库，以允许对入组受试者进行进一步随访，对选定受试者进行肝活检，并添加仔细定义的对照以及其他NAFLD受试者。其基本原理是明确评估疾病的自然史，开发和验证生物标志物并完成辅助研究，尽管使用了当前数据库，但这些研究仍然动力不足，（2）完成已启动的众多初步和辅助研究，（3）在NASH成人和儿童中进行额外的治疗试验。具体的研究将基于从各个中心收到的建议，这些建议得到了NASH CRN指导委员会和NIDDK的批准，并获得了资金，以及（4）进行各个中心提出的新的辅助研究。该中心提出了两项研究：（a）验证NASH的代谢组学特征。初步研究已经确定了NASH的独特脂质组学特征，（B）对BMI在30-45之间的NASH成人患者进行腹腔镜可调节带胃成形术（LABG）的随机对照试验。本试验将检验LABG是NASH安全有效治疗的假设。总之，所有这些研究都与NIH NAFLD肝脏行动计划直接一致。 公共卫生相关性：（申请人提供）：NAFLD和NASH是重要的健康问题，预计其发病率将增加。在最初的资助期间，CRN为NAFLD和NASH领域做出了重要贡献，但仍然存在许多未回答的问题。在下一个资助期内，CRN将继续研究NASH和相关疾病的风险因素、临床方面、自然史和最佳治疗方法