San Diego Cirrhosis Clinical Research Network

圣地亚哥肝硬化临床研究网络

基本信息

批准号：
10310901
负责人：
ROHIT LOOMBA
金额：
$ 35.21万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-09 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10310901
关键词：
Address Alcohols Ancillary Study Antineoplastic Agents Area Ascites California Cardiovascular system Cause of Death Cessation of life Chemopreventive Agent Chronic Hepatitis C Cirrhosis Clinical Clinical Research Clinical Trials Design Cohort Studies Consent County Data Death Rate Development Diagnosis Disease Disease Progression Dose Double-Blind Method Etiology Event Fibrosis Future General Population Genetic Risk HIV Hemorrhage Hepatic Hepatic Encephalopathy Hepatitis B Virus Hepatitis C virus Hepatology Hepatorenal Syndrome Hispanics Hospitalization Intervention Liver Liver Cirrhosis Liver diseases Malignant neoplasm of liver Measures Medical Meta-Analysis Monitor Multi-Institutional Clinical Trial Natural History Not Hispanic or Latino Outcome Outcome Measure Participant Patient Recruitments Patients Peritonitis Pharmacogenetics Phase Placebos Population Research Positioning Attribute Prevalence Primary carcinoma of the liver cells Property Protocols documentation Randomized Controlled Trials Research Research Infrastructure Risk Safety Site Testing Time United States United States National Institutes of Health Virus Diseases Work adjudicate atorvastatin clinical infrastructure cohort effective therapy efficacy evaluation genetic risk factor gut microbiome health disparity high risk imaging biomarker lipophilicity liver transplantation men microbiome microbiome signature mortality mortality risk multi-ethnic non-invasive imaging nonalcoholic steatohepatitis novel therapeutics patient population pleiotropism primary endpoint primary outcome prospective randomized trial recruit response secondary outcome treatment response

项目摘要

PROJECT SUMMARY This application is in response to RFA-DK-20-003, which is a limited competition opportunity with the objective of establishing the Liver Cirrhosis Network (LCN). Cirrhosis has doubled in prevalence in the last decade and is now the 11th leading cause of death in the United States. The number of cirrhosis-related deaths is projected to triple by 2030, with NASH projected to overtake HCV as the leading cause of liver transplantations. Severe limits on the number of liver transplantations performed each year and anticipated increases in the cirrhosis patient population create an urgent need to better understand predictors of mortality in cirrhosis and develop effective therapies to treat cirrhosis. Studies from our group and others suggest statins may reduce future risk of HCC and decompensation in patients with cirrhosis. Among statins, lipophilic statins such as atorvastatin have shown the greatest chemopreventive effects against HCC occurrence. Atorvastatin is associated with dose-dependent reduction in incident cirrhosis in HCV patients. Data supporting statin use for cirrhosis are promising, but larger, randomized controlled trials (RCT) are needed to determine whether they may be routinely recommended. To address the needs of the cirrhosis patient population, this research plan proposes the following aims: Aim 1: To conduct a prospective, longitudinal, multicenter, multi-ethnic cohort study of patients with cirrhosis. Among Hispanic men, cirrhosis is the 6th leading cause of mortality. To address this health disparity, we will test the hypothesis that Hispanic patients with cirrhosis are at higher risk for hepatic decompensation compared to non-Hispanics. We will establish and monitor a cohort of patients who have cirrhosis due to multiple etiologies. Primary endpoints include (a) a composite endpoint of hepatic decompensation, (b) liver transplantation, or (c) all–cause mortality. Ancillary studies will investigate associations between non-invasive imaging biomarkers, cirrhosis genetic risk score, and risk of decompensation. Following up on our previous work, we will also identify a microbiome signature that may predict decompensation risk. Aim 2: Phase 2, multi-center, double-blind, placebo-controlled, RCT evaluating efficacy and safety of atorvastatin 20 mg in subjects with compensated cirrhosis. The objective is to test the hypothesis that atorvastatin is more effective than placebo in reducing risk of decompensation, all-cause mortality and other liver-related clinical outcomes in cirrhosis patients. Primary outcome measure will be time to the first occurrence of any of the following adjudicated events: all-cause mortality, MELD score ≥ 15, liver transplant, ascites requiring medical intervention, hospitalization for onset of variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, and development of hepatocellular carcinoma. Secondary outcomes include safety of atorvastatin, decrease in fibrosis, as measured by NITs and imaging biomarkers, and major adverse cardiovascular events. Exploratory analyses will investigate associations between treatment response and (a) delta MRE and VCTE, (b) genetic risk factors, and (c) changes in the gut microbiome.

项目摘要该应用是响应RFA-DK-20-003，这是与Objectivese的有限竞争机会建立肝硬化网络（LCN）。现在，美国的第11大死亡原因。到2030年，纳什（Nash）预计将超过HCV作为严重限制的主要原因每年进行肝移植的数量，并预计肝硬化患者会增加人口迫切需要更好地了解肝硬化死亡率的预测指标并发展有效我们小组和其他他汀类药物的研究可能会降低未来的HCC未来风险肝硬化患者的代偿作用。针对HCC的最大化学预防作用。 HCV患者的入射肝硬化。需要随机对照试验（RCT）来确定他们是否是否满足肝硬化人群的需求，本研究计划提出了以下目的：目标1：对肝硬化患者进行前瞻性，纵向，多中心，多族裔队列研究。在西班牙裔男子中，肝硬化是死亡率的第六个主要原因。与肝硬化患者相比非西班牙裔。主要终点包括（a）肝功能补偿的复合终点，（b）肝移植或（c）全因疗法研究将调查非侵入性成像生物标志物之间的关联肝硬化的遗传风险评分和代偿性的风险。一个微生物组的标志，可以预测代理风险2：阶段2，多中心，双盲安慰剂对照，RCT评估Atorvastatin 20 mg的受试者的Atorvastatin 20 mg 补偿性肝硬化。为了降低代偿性的风险，全因死亡率和其他与肝脏相关的临床结果患者的主要结局措施将是以下裁决事件的第一次发生：全因死亡率，梅尔德评分≥15，肝移植，需要医疗国际的屁股，住院治疗静脉曲张出血，肝性脑病，自发性腹膜炎的发作和发育肝细胞癌。由NIT和成像生物标志物以及主要的不良心血管事件。治疗反应与（a）Delta MRE和VCTE之间的关联，（b）遗传危险因素以及（c）变化在肠道微生物组中。