FENOFIBRATE FOR TREATMENT OF NASH: A RANDOM, DOUBLE BLIND, PLACEBO-CTRLD STUDY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。非酒精性脂肪性肝炎（NASH）的特点是肝脏脂肪浸润并伴有炎症，可发展为不同程度的纤维化和肝硬化。目前还没有已知的治疗NASH的方法，尽管目前正在进行几项研究。有证据表明，胰岛素抵抗是NASH脂肪肝发病的关键因素。我们假设使用非诺贝特可以改善胰岛素抵抗，减少肝脏脂肪，并改善NASH的组织学严重程度。我们希望评估非诺贝特对NASH组织学改善的影响，并评估非诺贝特对NASH患者的安全性。我们计划进行一项双盲安慰剂对照研究，受试者将接受为期一年的研究药物（非诺贝特或安慰剂）治疗，并在治疗前和48周治疗结束时对肝脏进行组织学评估，以评估组织学改善。其他测试将包括使用间接量热法研究全脂氧化、葡萄糖耐量和DEXA扫描来评估非诺贝特治疗前后的腹部脂肪。在治疗过程中，每隔1 - 2个月通过访谈和抽血对患者进行评估。这项研究将包括所有性别和种族；有生育潜力的受试者将接受妊娠筛查。招聘将以先到先得的方式进行。研究记录将被编码并保存在一个上锁的文件柜中，从受试者那里获得的数据仅供调查人员链接。

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 characterized by fatty infiltration of the liver accompanied by inflammation which can progress to varying degrees of fibrosis and cirrhosis. There is currently no known treatment for NASH, though several studies are being currently conducted. There is evidence that insulin resistance is a key factor in the pathogenesis of fatty liver in NASH. We hypothesize that the use of fenofibrate improves insulin resistance, decreases liver fat, and improves the histologic severity of NASH. We hope to asses the effect of fenofibrate on the histologic improvement of NASH and to assess the safety of fenofibrate in patients with NASH. We plan to conduct a double-blind, placebo controlled study where the subject will undergo a one-year treatment with the study medication (fenofibrate or placebo) with histologic evaluation of the liver before treatment and at the end of 48 weeks of therapy in the study in order to assess histologic improvement. Other tests will include whole fat oxidation using indirect calorimetry study, glucose tolerance, and a DEXA scan to assess abdominal fat before and following fenofibrate treatment. During treatment, patients will be evaluated every one to two months by interview and blood draw as indicated in the protocol. The study will include all genders and races; subjects with child bearing potential will receive pregnancy screening. Recruitment will be on a first come-first serve basis. Research records will be coded and kept in a locked file cabinet, data acquired from the subjects will only be linkable by the investigators.