Silymarin for the Treatment of Nonalcoholic Steatohepatitis

水飞蓟素治疗非酒精性脂肪性肝炎

• 批准号: 8128338
• 负责人: VICTOR J NAVARRO
• 金额: $ 8.24万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8128338
• 关键词: Address; Adverse event; Ancillary Study; Anthropometry; Antioxidants; Area; Biopsy; Disease; Dose; Double-Blind Method; Drug Kinetics; Effectiveness; Enzymes; Exposure to; Fatty Liver; Fatty acid glycerol esters; Glimepiride; Half-Life; Hepatic; Histology; Hour; Hypoglycemic Agents; Incidence; Injury; Insulin; Insulin Resistance; Leptin; Lipids; Liver; Liver diseases; Magnetic Resonance Imaging; Malondialdehyde; Maximum Tolerated Dose; Measurement; Measures; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Outcome Measure; Oxidants; Patients; Phase; Placebo Control; Placebos; Population; Process; Property; Research; Research Design; Research Personnel; Risk; Role; Safety; Serum; Silymarin; Sulfonylurea Compounds; Time; Tumor Necrosis Factor-alpha; adiponectin; cytokine; design; diabetic; diabetic patient; effective therapy; efficacy trial; improved; indexing; nateglinide; non-diabetic; nonalcoholic steatohepatitis; phase 1 study; phase 2 study; programs; public health research; randomized trial; repaglinide; secondary outcome; silibinin; week trial

DESCRIPTION (provided by applicant): Non-alcoholic steatohepatitis (NASH) is an important cause of liver related morbidity. Given that obese and type 2 diabetic patients are at risk and these processes are common in the U.S., the impact of research aimed at finding a therapy is far reaching. By virtue of its antioxidant properties, Silymarin may have a plausible role as an effective therapy for NASH, a process in which oxidant injury has been implicated. Therefore, the broad aims of this research are to establish the safety, tolerability, and efficacy of Silymarin in NASH patients with two of the most commonly associated disorders, obesity and type 2 diabetes. The first part of the Phase I study is a dose-finding study using a sequence of escalating doses with alternating groups of obese patients with NASH. This study design aims to assess the safety, tolerability, and pharmacokinetic profile of silibinin at steady state conditions at a maximally tolerated dose of Silymarin. The primary endpoints of this study will be the incidence of adverse events and the pharmacokinetic parameter of AUC(0-12hr). The second part of phase I will assess the safety and tolerability of Silymarin in type 2 diabetics with NASH, studied separately from the obese patients due to the potential interacting effect of oral hypoglycemics. Specifically, we will compare the pharmacokinetic parameter of AUC(0-12hr) and the incidence of adverse events in obese patients with NASH to type 2 diabetics with NASH who are treated with oral secretagogues (sulfonylureas, repaglinide, nateglinide, glimepiride) with or without insulin. The phase II study will comprise a 48 week placebo controlled double blind randomized trial of Silymarin in patients with NASH and obesity or type 2 diabetes. The primary endpoint will be the improvement in hepatic histology, compared to baseline, in Silymarin versus placebo treated patients. Relevance to Public Health: This research addresses an increasingly common problem in a large segment of the U.S. population; that is, liver injury caused by fat in obese and diabetic patients. Silymarin has been used for many centuries for the treatment of liver diseases and has been shown to be safe. This research will prove the safety and effectiveness of Silymarin for liver injury caused by fat in obese and diabetic patients, in carefully designed scientific trials. These results will allow practitioners and patients to decide whether to use Silymarin in this specific disease process.

描述（由申请人提供）：非酒精性脂肪性肝炎（NASH）是肝相关发病率的重要原因。鉴于肥胖和2型糖尿病患者处于危险之中，并且这些过程在美国很常见，因此旨在寻找治疗疗法的研究的影响已达到远处。凭借其抗氧化特性，水莲蛋白可能作为NASH的有效疗法具有合理的作用，这一过程已涉及氧化剂损伤。因此，这项研究的广泛目的是建立水远二来酰蛋白在患有两种最常见疾病的NASH患者中的安全性，耐受性和功效。第一阶段研究的第一部分是一项剂量调查研究，使用一系列与NASH的肥胖患者组成的剂量逐步升级。这项研究设计旨在评估在稳态条件下，在最大耐受剂量的水莲蛋白下，在稳态条件下，硅蛋白的安全性，耐受性和药代动力学特征。这项研究的主要终点是不良事件的发生率和AUC的药代动力学参数（0-12hr）。第一阶段的第二部分将评估由纳什（Nash）在2型糖尿病患者中的安全性和耐受性，由于口服低糖的潜在相互作用效果，与肥胖患者分开研究。具体而言，我们将比较AUC（0-12hr）的药代动力学参数以及NASH肥胖患者的不良事件与2型糖尿病患者的纳什（NASH）的2型糖尿病患者（sulfonylureas，sulfonylureas，repagaglinide，repagaglinide，repagaglinide，nateginide，glimepride，glimepride，glimepride）具有或无胰岛素。第二阶段的研究将包括一项为期48周的安慰剂对照双盲随机试验，对纳什和肥胖症患者或2型糖尿病患者。主要终点是与基线相比，是肝林与安慰剂治疗的患者相比的肝组织学的改善。 与公共卫生有关：这项研究解决了在美国大部分地区越来越普遍的问题；也就是说，肥胖和糖尿病患者脂肪造成的肝损伤。水莲林已被用于治疗肝病，并被证明是安全的。在精心设计的科学试验中，这项研究将证明是由肥胖和糖尿病患者脂肪引起的脂肪损伤的安全性和有效性。这些结果将使从业人员和患者可以决定是否在此特定疾病过程中使用水硅林。