Cholestasis Reversal (Phase ll): Efficacy of lV Fish Oil

描述（由申请人提供）： 肠外营养（PN）解决方案是外科胃肠道疾病患者的生命挽救。 然而，在儿科人群（尤其是早产儿）中使用PN通常与肝损伤相关，肝损伤可能最终导致肝衰竭，肝衰竭可能导致移植和/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。 最近的经验表明，停止基于大豆的IFE并改用由鱼油（Omegaven）衍生的omega-3脂肪酸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。 2002年，美国国家糖尿病、消化和肾脏疾病研究所（NIDDK）指出，美国有20，000人因肠衰竭接受PN治疗，其中约30-60%的儿童在接受长期PN治疗后发生肝功能障碍。 本项目计划在3年内研究30例因PN使用而既存肝病的儿科患者。 主要目的是评估鱼油脂肪乳剂在逆转PN所致胆汁淤积方面的疗效。 采用开放标签研究设计，PN胆汁淤积患者将停用传统大豆油脂肪乳剂，并接受基于鱼油的IFE治疗。 将鱼油治疗受试者的胆汁淤积逆转时间与60例在发生胆汁淤积后继续接受大豆IFE的相似受试者（同期历史对照）进行比较。 还将评估其他肝脏、生长和安全性结局。 根据初步结果，很难对这些患者进行前瞻性随机试验。 虽然这项研究不是随机试验，但人们认为可以产生足够的证据，导致FDA批准Omegaven等lFE。

DESCRIPTION (provided by applicant): Parenteral nutrition (PN) solutions are life saving in patients with surgical gastrointestinal diseases. However, the use of PN in pediatric populations, especially premature infants, is frequently associated with liver injury that may ultimately result in liver failure that can lead to transplantation and/or death. Studies suggest that soybean oil containing intravenous fat emulsions (IFE) may be a major contributing factor. Recent experience suggests that discontinuing soybean based IFE and switching to a product comprised of omega-3 fatty acids derived from fish oils (Omegaven) may be effective in reversing preexisting PN associated liver disease through a combination of factors, including improved triglyceride clearance coupled with anti-inflammatory properties. In 2002, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) stated that 20,000 individuals in the US were supported by PN for intestinal failure and of these, approximately 30-60% of children develop hepatic dysfunction after receiving prolonged courses of PN. This project plans to study 30 such pediatric patients over a 3 year period with preexisting liver disease due to PN use. The primary aim is to assess the efficacy of the fish oil fat emulsion in reversing cholestasis due to PN use. Using an open label study design, patients with PN cholestasis will have the conventional soybean oil lipid emulsion stopped and be treated with the fish oil based IFE. Time to reversal of cholestasis of subjects treated with the fish oil will be compared to 60 similar subjects (contemporary historical controls) who continued to receive soybean based IFE after developing cholestasis. Other hepatic, growth, and safety outcomes will be also assessed. Based on preliminary results, it would be difficult to perform a prospective randomized trial with these patients. Although the proposed study is not a randomized trial, it is thought that sufficient evidence could be generated that would result in FDA approval of an lFE such as Omegaven.