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发育障碍。鉴于克罗恩病发病率的上升和早期诊断，营养和发育对这些儿童来说是至关重要的结果。关于这些参数对克罗恩病新疗法的反应，目前还缺乏相关知识。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顽固性或合并瘘管性疾病的克罗恩病儿童的护理。我们假设活动期克罗恩病儿童的能量消耗和蛋白分解增加，英夫利昔单抗治疗将导致这些参数比传统的皮质类固醇治疗有更大的改善。为了验证这些假说，患有活动性复发性克罗恩病的儿童将参加一项前瞻性研究。门诊代谢研究将在英夫利昔单抗皮质类固醇治疗开始前、两周和十四周后进行。使用稳定的必需氨基酸同位素，可以在禁食、肠内和肠外喂养状态下测量全身蛋白质分解和白蛋白合成的速率。每次就诊时，使用间接量热法计算静息能量消耗，使用双标签水计算总能量消耗。这项拟议的工作是创新的，因为它扩大了蛋白质和能量使用的知识，以应对儿童克罗恩病的传统和新疗法。这些结果还将有助于克隆氏病儿童发挥其真正的成长潜力。首席研究员在完成临床研究理学硕士学位后，在儿童代谢研究方面经验丰富的赞助商的支持下，处于既定的临床研究环境中。未来计划进行营养和代谢技术方面的培训，以促进首席研究人员的教育。这项研究将使首席研究人员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人员扩大这些研究。

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.