Cholestasis Prevention: Efficacy of IV Fish Oil

描述（由申请人提供）： 尽管肠外营养（PN）是必需的，但在患有外科胃肠道疾病的儿科人群（尤其是早产儿）中使用PN通常与肝功能障碍相关，最终可能导致移植和/或死亡。研究表明，含有大豆油的静脉脂肪乳剂（IFE）可能是一个主要的影响因素。 初步数据表明，停止基于大豆的IFE并改用由鱼油衍生的omega-3脂肪酸（FA）组成的产品可能通过多种因素的组合（包括改善甘油三酯清除率以及抗炎特性）有效逆转既存PN相关肝病。 申请人认为，鱼油乳剂除了治疗这种致命疾病外，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择30名在PN疗程开始时患有胃肠道疾病的婴儿（< 3个月），接受鱼油乳剂PN（15名患者）或标准护理大豆乳剂PN（15名患者）。 预计接受PN治疗至少3个月的患者将在3年内入组。 为了评价这种替代IFE的有效性，将对两个研究人群的肝功能常规生化检查进行评估和比较。 主要结果将是三个月内发生胆汁淤积的儿童比例。 除了预防肝脏疾病的发展外，还希望儿童能够继续以相同的速度生长，或者比他们接受标准脂肪乳剂时更好。 将评估的其他长期结局包括炎症性疾病的频率，包括这些危重婴儿经常发生的支气管肺发育不良（BPD）和早产儿视网膜病变（ROP）。 该项目的最终目标是证明鱼油乳剂可获得FDA批准用于依赖PN的儿童，同时从手术胃肠道疾病中恢复。 使用PN和鱼油基乳剂可预防肝功能障碍，从而通常改善这些儿童的健康结局。

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.