Gender Differences in Growth in Pediatric Patients with Crohn's Disease

描述(由申请人提供)： 这是加州大学旧金山分校的儿科胃肠病专家尼拉·古普塔博士的K23奖项的申请。古普塔博士在以患者为导向的儿科炎症性肠病(IBD)临床研究中确立了自己作为年轻研究员的地位。这一K23奖项将为古普塔博士提供必要的支持，以实现以下目标：(1)成为儿童IBD临床研究方面的专家；(2)对IBD儿童患者的生长发育的内分泌方面进行临床调查；(3)在临床研究中应用先进的生物统计学方法；(4)开发和维护包含多个站点数据的关系数据库；以及(5)发展独立的临床研究事业。为了实现这些目标，Gupta博士组建了一个指导团队，成员包括一位主要导师、加州大学旧金山分校儿科胃肠病培训项目主任Melvin Heyman博士、以及三位共同导师：Robert Lustig博士，专注于下丘脑功能及其生长和能量平衡调节的内分泌学家；Eric Vittinghoff博士，研究设计与当前最先进的生物统计学方法的专家；Michael Kohn博士，他在数据库开发和管理方面具有专业知识。 生长发育障碍是克罗恩病公认的并发症。古普塔博士的研究将集中在新诊断的克罗恩病儿童患者的身高和生长速度z分数上的性别和年龄的相对影响(目标1)，以及性别、青春期发育(Tanner阶段)和疾病活动对克罗恩病儿童患者生长激素/胰岛素样生长因子I水平和身高z分数的相对影响(目标2)。在目标1中，古普塔博士将使用儿科IBD联盟(由美国6个不同地区的中心组成)的现有基础设施来登记和跟踪200名新诊断的克罗恩病儿童患者，以确定疾病表现和诊断时性别和年龄对生长的独立影响。在目标2中，古普塔博士将进行一项单中心横断面初步研究，以产生有关性别、青春期状况和疾病严重程度对克罗恩病儿童生长发育影响的初步数据。这两项研究都将利用先进的多变量统计方法。这项研究将为新诊断的儿童克罗恩病的多中心纵向研究奠定基础，该研究将在K奖结束前提出R01拨款申请。 公共卫生相关性：更好地了解克罗恩病儿童患者生长发育障碍的病因和性别相关差异，对于确定有效的医疗管理策略至关重要，并可能澄清这种慢性疾病过程中性别差异的潜在机制。

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Neera Gupta, a pediatric gastroenterologist at the University of California, San Francisco. Dr. Gupta is establishing herself as a young investigator in patient-oriented clinical research of pediatric inflammatory bowel disease (IBD). This K23 award will provide Dr. Gupta with the support necessary to accomplish the following goals: (1) to become expert at patient-oriented clinical research in pediatric IBD; (2) to conduct clinical investigations of endocrinologic aspects of growth in pediatric patients with IBD; (3) to implement advanced biostatistical methods in clinical studies; (4) to develop and maintain a relational database containing data from multiple sites; and (5) to develop an independent clinical research career. To achieve these goals, Dr. Gupta has assembled a mentoring team comprised of a primary mentor, Dr. Melvin Heyman, Director of the Training Program in Pediatric Gastroenterology at UCSF, who conducts clinical investigations in pediatric IBD, and three co-mentors: Dr. Robert Lustig, an endocrinologist who focuses on hypothalamic function and its regulation of growth and energy balance; Dr. Eric Vittinghoff, an expert in study design and current state-of-the-art biostatistical methods; and Dr. Michael Kohn, who has expertise in database development and management. Growth impairment is a well-recognized complication of Crohn's disease. Dr. Gupta's research will focus on the relative influence of gender and age at disease presentation and diagnosis on height and growth velocity z scores in newly diagnosed pediatric patients with Crohn's disease (Aim 1) and the relative effects of gender, pubertal development (Tanner stage) and disease activity on growth hormone/insulin-like growth factor I levels and height z scores in pediatric patients with Crohn's disease (Aim 2). In Aim 1, Dr. Gupta will use the existing infrastructure of the Pediatric IBD Consortium (composed of centers in 6 geographically distinct US regions) to enroll and follow 200 newly-diagnosed pediatric patients with Crohn's disease to determine the independent effects of gender and age at disease presentation and diagnosis on growth. In Aim 2, Dr. Gupta will conduct a single-center cross-sectional pilot study to generate preliminary data on the effects of gender, pubertal status, and disease severity on growth in children with Crohn's disease. Both studies will utilize advanced multivariate statistical methods. This research will form the basis for a multicenter longitudinal study in newly diagnosed childhood Crohn's disease, to be proposed in an R01 grant application before the end of the K award. Public health relevance: Improved understanding of the etiology and gender-associated differences in growth impairment in pediatric patients with Crohn's disease is critical to determine effective medical management strategies and may clarify the underlying mechanisms for gender differences in the course of this chronic disorder.