Protein and Energy Use in Pediatric Crohn's Disease

描述（由申请人提供）： 超过三分之一的克罗恩病儿童患有生长障碍。 鉴于克罗恩病的发病率上升和早期诊断，营养和生长是这些儿童的关键结果。 目前缺乏关于这些参数对克罗恩病新疗法的反应的知识。 英夫利昔单抗是一种抗肿瘤坏死因子-α抗体，它彻底改变了对皮质类固醇治疗无效或并发瘘管病的克罗恩病患儿的治疗。 我们假设活动性克罗恩病患儿的能量消耗和蛋白水解增加，与传统的皮质类固醇治疗相比，英夫利西单抗治疗将导致这些参数的更大改善。 为了验证这些假设，将在一项前瞻性研究中招募活动性复发性克罗恩病儿童。 将在开始皮质类固醇或英夫利西单抗治疗前、两周和十四周进行门诊患者代谢研究。 使用稳定的必需氨基酸同位素，可以在禁食、肠内和胃肠外进食状态下测量全身蛋白水解和白蛋白合成的速率。 将在每次访视时计算静息能量消耗（使用间接热量测定法）和总能量消耗（使用双标记水）。 拟议的工作是创新的，因为它扩展了蛋白质和能量使用的知识，以应对儿科克罗恩病的传统和新型疗法。 这些结果也将有助于克罗恩病儿童达到他们真正的生长潜力。主要研究者已获得临床研究理学硕士学位，与在儿童代谢研究方面经验丰富的申办者一起在既定的临床研究环境中工作。 未来的营养和代谢技术培训计划进一步的主要研究者的教育。 本研究将使主要研究者有机会在指导环境中继续发展临床研究技能，并期望在未来作为独立研究者扩展这些研究。

DESCRIPTION (provided by applicant): More than one-third of children with Crohn's disease suffer from growth failure. Given the rising incidence and earlier diagnosis of Crohn's disease, nutrition and growth are critical outcomes for these children. There is a lack of knowledge concerning the response of these parameters to new therapies for Crohn's disease. Infliximab, an anti-tumor necrosis factor-alpha antibody, has revolutionized the care of children with Crohn's disease recalcitrant to corticosteroid therapy or complicated by fistulizing disease. We hypothesize that children with active Crohn's disease will have increased energy expenditure and proteolysis, and that treatment with infliximab will lead to greater improvement in these parameters than traditional corticosteroid therapy. To test these hypotheses, children with active relapsed Crohn's disease will be enrolled in a prospective study. Outpatient metabolic studies will be conducted just before, tow and fourteen weeks after initiation of corticosteroid of infliximab therapy. Using stable essential amino acid isotopes, rates of total body proteolysis and albumin synthesis can be measured in fasting, and enterally and parenterally fed states. Resting energy expenditure, using indirect calorimetry, and total energy expenditure, using doubly-labeled water, will be calculated at each visit. The proposed work is innovative, as it expands the knowledge of protein and energy use in response to traditional and novel therapies for pediatric Crohn's disease. These results will also help allow children with Crohn's disease to reach their true growth potential. The principal investigator, having completed a Masters of Science in Clinical Research, is in an established clinical research environment with a sponsor experienced in metabolic studies in children. Future training in nutrition and metabolic techniques are planned to further the principal investigator's education. This study will allow the principal investigator the opportunity to continue to develop clinical research skills in a mentored environment, with the expectation to expand these studies as an independent investigator in the future.