METABOLIC RESPONSE TO INFLIXIMAB IN PEDIATRIC ULCERATIVE COLITIS

小儿溃疡性结肠炎对英夫利昔单抗的代谢反应

• 批准号: 7379157
• 负责人: STEVEN J STEINER
• 金额: $ 0.02万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379157
• 关键词: METABOLIC; RESPONSE; INFLIXIMAB; PEDIATRIC; ULCERATIVE

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. Acute exacerbations of ulcerative colitis lead to negative energy and protein balances, which may contribute to malnutrition, growth retardation and poor healing. Infliximab, an anti-tumor necrosis factor (TNF)- antibody, has been efficacious in children with steroid-resistant ulcerative colitis. The objective of this application is to characterize protein and energy metabolism and their response to anti-TNF- therapy in children with active ulcerative colitis in both the fasting and parenterally fed states. The central hypothesis of this application is that inflammatory cytokines present in ulcerative colitis, including TNF- , increase net protein catabolism and resting energy expenditure and that anti-TNF- therapy will result in improvement in these metabolic measurements. Our long-range goal is to optimize the nutritional and growth outcomes of children with ulcerative colitis. Children with steroid-resistant ulcerative colitis who have been scheduled for their initial dose of infliximab will be recruited for this study. To accomplish the objectives of our aims, these children will be studied just prior to and two weeks following their initial dose of infliximab. Using stable isotope techniques, we will measure protein kinetics and balance during both the fasting state and parenteral nutrition infusion. Using indirect calorimetry, resting energy expenditure will be determined during fasting and parenteral nutrition infusion. The proposed work is innovative, because it expands our knowledge of the utilization of nutrition in ulcerative colitis. It is our expectation that this approach will more clearly delineate the underlying causes of growth disturbance in children with ulcerative colitis.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。溃疡性结肠炎的急性加重会导致能量和蛋白质的负平衡，这可能会导致营养不良、生长迟缓和愈合不良。英夫利昔单抗是一种抗肿瘤坏死因子(TNF)抗体，对激素抵抗型溃疡性结肠炎儿童有效。这项应用的目的是研究儿童活动期溃疡性结肠炎患者在禁食和非肠道喂养状态下的蛋白质和能量代谢及其对抗肿瘤坏死因子治疗的反应。这一应用的中心假设是，溃疡性结肠炎中存在的炎性细胞因子，包括肿瘤坏死因子-，增加了净蛋白质分解代谢和静息能量消耗，抗肿瘤坏死因子治疗将导致这些代谢测量的改善。我们的长期目标是优化溃疡性结肠炎儿童的营养和生长结果。计划接受英夫利昔单抗初始剂量的类固醇抗药性溃疡性结肠炎的儿童将被招募参加这项研究。为了实现我们的目标，这些儿童将在首次服用英夫利昔单抗之前和之后的两周内进行研究。使用稳定同位素技术，我们将测量禁食状态和肠外营养输注期间的蛋白质动力学和平衡。采用间接量热法，测定空腹和肠外营养输注期间的静息能量消耗。这项拟议的工作是创新的，因为它扩大了我们对溃疡性结肠炎营养利用的了解。我们期望这一方法将更清楚地描述溃疡性结肠炎儿童生长障碍的潜在原因。