PIOGLIATAZONE VERSUS VITAMIN E VERSUS PLACEBO FOR THE TREATMENT OF NONDIABETI

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。非酒精性脂肪性肝炎（NASH）是一种慢性肝病，可进展为肝硬化、肝衰竭和肝细胞癌。发展NASH的最重要的风险因素之一是肥胖。由于肥胖的持续流行，NASH的发病率正在迅速增加。目前，尚无针对NASH的有效治疗方法。迄今为止的研究表明，胰岛素抵抗和氧化应激在NASH的发病机制中起重要作用。NASH临床研究网络（NASH CRN）是NIH资助的网络，成立于2002年，印第安纳州大学是其临床中心之一。NASH CRN拟开展PIVENS试验，这是一项多中心、随机、双盲、安慰剂对照研究，旨在评价吡格列酮（胰岛素增敏剂）或维生素E（抗氧化剂）给药96周治疗非糖尿病个体NASH的疗效。主要终点是NASH活性的改善，其定义为基线和治疗96周后肝活检标准化评分的变化。总样本量为240例患者，该中心最多可入组50例患者。所有的统计分析将由约翰霍普金斯公共卫生学院的数据协调中心完成。NIDDK指定的DSMB将监测肝毒性、低血糖、妊娠、新发糖尿病等结局的安全性和疗效数据，以及确定为安全性相关的任何其他结局或事件。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Non-alcoholic steatohepatitis (NASH) is a chronic liver disorder and can progress to cirrhosis, liver failure and hepatocellular cancer. One of the most important risk factors to develop NASH is obesity. Due to the ongoing epidemic of obesity, the incidence of NASH is increasing rapidly. At the current time, there are no proven treatments for NASH. Studies done to date suggest that insulin resistance and oxidative stress play an important role in the pathogenesis of NASH. NASH Clinical Research Network (NASH CRN) is an NIH funded network that was established in 2002 and Indiana University is one of its clinical centers. NASH CRN is proposing to conduct the PIVENS trial which is a multicenter, randomized double-masked, placebo-controlled study that evaluates the efficacy of pioglitazone (insulin sensitizer) or vitamin E (antioxidant) administered for 96 weeks to treat NASH in individuals without diabetes. The primary endpoint is improvement in NASH activity defined from change in standardized scoring of liver biopsies at baseline and after 96 weeks of treatment. Total sample size is 240 patients and this center may enroll up to 50 patients. All of the statistical analyses will be done by the Data Coordinating Center at the Johns Hopkins School of Public Health. NIDDK appointed DSMB will monitor the data for safety and efficacy for outcomes such as hepatotoxicity, hypoglycemia, pregnancy, new onset diabetes, and any other outcomes or events identified as safety-related.