Efficacy of enteral glutamine in reducing bloodstream infections in SBS infants

描述（由申请人提供）：在各种情况下，特别是坏死性肠结肠炎（NEC）的大量肠切除术后出现短肠综合征（SBS），是一种破坏性并发症，影响新生儿，特别是那些分娩< 36周胎龄的新生儿。这些儿童特别容易发生复发性血流感染（BSI）、反复住院和随后的生长不良。所有这些都给初级护理人员和卫生保健系统造成了非常沉重的负担。与这些儿童复发性BSI相关的微生物主要与肠道有关。然而，对于这些儿童的肠道微生物生态，以及它是否在BSI、肠内喂养和最终生长中发挥作用，目前还缺乏了解。在成人SBS患者中，补充谷氨酰胺（GLN）已被证明可以减少粘膜损伤，降低BSI和相关败血症的发生率，并改善正氮平衡。在儿童中，目前没有足够的数据来确定肠内补充GLN是否能改善因胃肠切除术导致SBS的婴儿的临床结果。本试点临床研究的总体目的是在一项严格的双盲探索性临床试验的背景下，获得所需的初步数据，以了解肠内补充GLN对因NEC而进行重大肠道切除术的SBS儿童的疗效，具体目的如下：对因NEC而依赖pn的SBS患儿进行双盲、随机、安慰剂对照、为期6个月的初步研究，将肠内GLN （0.6g/kg）与等热量、等氮丙氨酸（安慰剂）治疗进行比较，以评估GLN降低BSI（主要终点）和血清TNF-、il - 1- 2、IL-6和IL-8浓度（次要终点）的疗效。特异性目标2：评估6个月肠内GLN治疗对目标1受试者的躯体生长参数[长度速度（主要终点）、体重速度和头围]的疗效，以及BSI对这些生长参数的影响。具体目标3：全面评估Aim 1 SBS患者与非SBS年龄匹配对照组（主要终点）的肠道肠道微生物组（使用最先进的分子方法），将肠道内存在的主要细菌动力学与特定微生物引起的BSI相关联，并探讨肠内GLN治疗是否会改变肠道肠道微生物组。该提案将促进由埃默里大学、密歇根大学和科罗拉多大学博尔德分校组成的多中心、多学科团队的发展，以评估降低BSI和促进生长的新方法，并深入了解SBS儿童的肠道微生物生态。

DESCRIPTION (provided by applicant): Short bowel syndrome (SBS) following massive bowel resection for various conditions, especially necrotizing entercolitis (NEC), is a devastating complication that affects neonates especially those delivered < 36 weeks gestational age. These children are especially susceptible to recurrent blood stream infections (BSI), repeated hospital admissions and subsequent poor growth. All of these contribute to a very high burden on the primary caretakers and the health care system. Organisms associated with recurrent BSI in these children are predominantly gut related. However, there is still a lack of understanding of the intestinal microbial ecology of these children and whether it has a role in BSI, enteral feeds and ultimately growth. Glutamine (GLN) supplementation has been shown in adults with SBS to decrease mucosal damage, lower rates of BSI and associated sepsis and improve positive nitrogen balance. In children, there is currently insufficient data to determine whether enteral GLN supplementation improves clinical outcomes in young infants with significant gastrointestinal resection leading to SBS. The overall purpose of this pilot clinical study is to obtain needed preliminary data on the efficacy of enteral GLN supplementation in children with SBS as a result of significant intestinal resection due to NEC in the context of a rigorous, double-blind exploratory clinical trial with the following specific aims: Specific Aim 1: To perform a double-blind, randomized, placebo controlled, 6-months pilot study of enteral GLN (0.6g/kg) vs. isocaloric, isonitrogenous alanine (placebo) treatment in PN-dependent SBS children due to NEC to evaluate the efficacy of GLN to decrease BSI (primary endpoint) and serial serum concentrations of TNF- , IL1- 2, IL-6 and IL-8 (secondary endpoint). Specific Aim 2: To assess the efficacy of 6 months of therapy with enteral GLN on somatic growth parameters [length velocity (primary endpoint), weight velocity and head circumference] in Aim 1 subjects and the impact of BSI on these growth parameters. Specific Aim 3: To comprehensively assess the gut lumenal microbiome (using state-of-the art molecular methods) in Aim 1 SBS patients versus non-SBS, age-matched control subjects (primary endpoint), to correlate major bacterial dynamics present in the lumen with BSI due to specific microbes and to explore whether the gut lumenal microbiome is altered by enteral GLN treatment. This proposal will facilitate the development of a multicenter, multidisciplinary team from Emory University, University of Michigan and University of Colorado at Boulder to assess new methods for decreasing BSI and improving growth as well as to gain insights into the intestinal microbial ecology of SBS children.