TRIAL OF BETAINE IN PTS WITH NONALCOHOLIC STEATOHEPATIS

甜菜碱治疗非酒精性脂肪肝患者的试验

• 批准号: 7605444
• 负责人: MANAL F. ABDELMALEK
• 金额: $ 0.59万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-23 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605444
• 关键词: Betaine; Clinic; Computer Retrieval of Information on Scientific Projects Database; Condition; Cystadane; End Point; Ethanolamines; Fatty acid glycerol esters; Fibrosis; Funding; Grant; Hepatocyte; Infiltration; Institution; Label; Lipid Peroxidation; Lipoproteins; Liver; Liver diseases; Medical; Metabolic; Methionine; Mitochondria; Patients; Pilot Projects; Placebos; Prevention; Production; Randomized; Reactive Oxygen Species; Research; Research Personnel; Resources; Safety; Source; Staging; Steatohepatitis; Test Result; United States National Institutes of Health; double-blind placebo controlled trial; ethanolamine; health related quality of life; improved; liver biopsy; non-alcoholic; nonalcoholic steatohepatitis; prevent

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. Nonalcoholic steatohepatitis (NASH) is an increasingly recognized clinic pathological condition that may progress to end-stage liver disease. No effective medical therapy is currently available for patients with NASH. Betaine is a normal component of the metabolic cycle of methionine and has been shown to increase S-adenosylmethionine levels (SAM). SAM converts phosphatidyl-ethanolamine to phophatidylcholine which is an important constituent of lipoproteins involved in the transport of fat from the liver, hence preventing the infiltration of fat into the liver and subsequent liver damage. By increasing SAM levels, betaine protects against fat accumulation within hepatocytes. Prevention of steatosis arrests mitochondria reactive oxygen species production and decreases lipid peroxidation, which in turn blocks progress along the continuum from steatosis to steatohepatitis to advanced fibrosis that occurs in patients with NASH. In an open label pilot study conducted by our group, we have previously shown that betaine significantly improves or normalizes abnormal liver test results, as well as liver histological damage in patients with NASH. The aim of the current study is to determine the efficacy and safety of betaine in a randomized, double-blind, placebo controlled trial. A total of 46 patients with NASH will be randomized to treatment with betaine (Cystadane¿) 20 g/d or an identical placebo for 12 months. The primary end-point will be changes in degree of steatosis, necroinflammatory activity and fibrosis on liver biopsy, whereas secondary end-points will be changes in liver test results and health related quality of life.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 非酒精性脂肪性肝炎（NASH）是一种日益被认识的临床病理状况，可能进展为终末期肝病。目前对于 NASH 患者尚无有效的药物治疗方法。甜菜碱是蛋氨酸代谢循环的正常成分，已被证明可以增加 S-腺苷蛋氨酸 (SAM) 水平。 SAM 将磷脂酰乙醇胺转化为磷脂酰胆碱，磷脂酰胆碱是参与肝脏脂肪运输的脂蛋白的重要组成部分，从而防止脂肪渗入肝脏和随后的肝脏损伤。通过增加 SAM 水平，甜菜碱可防止肝细胞内脂肪堆积。预防脂肪变性可以阻止线粒体活性氧的产生并减少脂质过氧化，从而阻止 NASH 患者从脂肪变性到脂肪性肝炎再到晚期纤维化的进展。在我们小组进行的一项开放标签试点研究中，我们之前已经表明甜菜碱可显着改善或正常化异常的肝脏测试结果以及 NASH 患者的肝脏组织学损伤。本研究的目的是通过随机、双盲、安慰剂对照试验确定甜菜碱的功效和安全性。总共 46 名 NASH 患者将被随机分配接受甜菜碱 (Cystadane¿) 20 g/天或相同的安慰剂治疗，为期 12 个月。主要终点是肝活检中脂肪变性程度、坏死性炎症活动和纤维化的变化，而次要终点是肝脏检测结果和健康相关生活质量的变化。