Cholestasis Prevention: Efficacy of IV Fish Oil

描述(由申请人提供)： 尽管肠外营养(PN)的使用是必要的，但在患有外科胃肠道疾病的儿童人群中，尤其是早产儿，使用PN往往与肝功能障碍有关，最终可能导致移植和/或死亡。研究表明，含有静脉脂肪乳剂(IFE)的大豆油可能是一个主要的致病因素。试点数据表明，停止使用以大豆为基础的IFE，改用由从鱼油中提取的omega-3脂肪酸(FAs)组成的产品，可能通过一系列因素，包括改善甘油三酯清除和抗炎特性，有效地逆转先前存在的PN相关性肝病。申请人认为，鱼油乳剂除了可以治疗这种致命的疾病外，还可以预防这种疾病。该项目计划在一项双盲研究中随机选取30名患有胃肠道疾病的婴儿(3个月)，在他们的PN疗程开始时，接受以鱼油为基础的乳剂(15名患者)或标准护理大豆乳剂(15名患者)的PN。预计至少接受PN治疗3个月的患者将在三年内入选。为了评估这种替代IFE的有效性，将在两个研究人群之间评估和比较肝功能的常规生化测试。主要结果将是儿童在三个月内出现胆汁淤积的比例。除了预防肝病的发展，人们希望孩子们继续以与接受标准脂肪乳剂相同的速度或更好的速度生长。其他将被评估的长期结果包括炎症性疾病的频率，包括支气管肺发育不良(BPD)和早产儿视网膜病变(ROP)，这些疾病经常发生在这些危重婴儿中。该项目的最终目标是证明鱼油乳剂可以被FDA批准用于依赖PN的儿童，同时从外科胃肠道疾病中恢复。使用鱼油乳剂的PN可以预防肝功能障碍，通常会对这些儿童产生更好的健康结果。

DESCRIPTION (provided by applicant): Although essential, the use of parenteral nutrition (PN) in pediatric populations with surgical gastrointestinal diseases, especially premature infants, is frequently associated with hepatic dysfunction that may ultimately result in transplantation and/or death. Studies suggest that soybean oil containing intravenous fat emulsions (IFE) may be a major contributing factor. Pilot data suggests that discontinuing soy based IFE and switching to a product comprised of omega-3 fatty acids (FAs) derived from fish oils may be effective in reversing preexisting PN associated liver disease through a combination of factors, including improved triglyceride clearance coupled with anti-inflammatory properties. The applicant believes that fish oil based emulsions, besides treating this fatal condition, could prevent it. This project plans to randomize in a double blind study 30 infants (< 3 months) with gastrointestinal disease at the start of their PN course to receive PN with a fish oil based emulsion (15 patients) or a the standard of care soybean based emulsion (15 patients). Patients expected to be on PN at least 3 months will be enrolled over three years. To evaluate effectiveness of this alternative IFE, conventional biochemical tests of hepatic function will be assessed and compared between the two study populations. The primary outcome will be the proportion of children developing cholestasis over a three month period. In addition to preventing the development of liver disease, it is hoped that the children will continue to grow at the same rate or better than if they were receiving the standard fat emulsion. Other long term outcomes that will be evaluated include the frequency of inflammatory diseases including bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) that often occur in these critically ill infants. The ultimate goal of this project is to demonstrate that fish oil based emulsions can be approved by the FDA for use in children dependent on PN to while recovering from surgical gastrointestinal diseases. Use of PN with fish oil base emulsion may prevent liver dysfunction resulting generally in better heath outcomes for these children.