Clinical Center: ChiLDReN (Childhood Liver Disease Research Network)

临床中心：ChiLDReN（儿童肝病研究网络）

• 批准号: 8773967
• 负责人: PETER Frank WHITINGTON
• 金额: $ 37.43万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8773967
• 关键词: Accounting; Affect; Alagille Syndrome; Animal Model; Area; Bile Acid Biosynthesis Pathway; Biliary Atresia; Biological; Biological Markers; Child; Childhood; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Cystic Fibrosis; Data; Databases; Defect; Development; Diagnosis; Disease; Education; Elements; Etiology; Fibrosis; Functional disorder; Future; Gene Expression; Genetic Predisposition to Disease; Goals; Hepatic; Incidence; Individual; Infant; Investigation; Leadership; Left; Link; Live Birth; Liver; Liver diseases; Measures; Mission; Mitochondria; Morbidity - disease rate; Names; Natural History; Other Genetics; Participant; Pathogenesis; Patients; Performance; Plasma; Principal Investigator; Process; Production; Progressive intrahepatic cholestasis; Public Health; Publishing; Records; Recruitment Activity; Research; Research Design; Research Methodology; Research Personnel; Resources; Role; Signal Transduction; Specimen; Staging; Testing; Therapeutic; Translational Research; United States; Work; alpha 1-Antitrypsin Deficiency; biobank; burden of illness; cohort; early childhood; epigenomics; expectation; fibrogenesis; improved; infancy; liver transplantation; mortality; neonatal hepatitis; neonate; novel; operation; osteopontin; outcome forecast; programs; public health relevance; research study; response; response to injury; smoothened signaling pathway; success

DESCRIPTION (provided by applicant): Liver disease is a major cause of infant and childhood morbidity and mortality. The diseases comprising "pediatric liver diseases" are individually rare, which has hindered the study of their causes/pathophysiologies. As a result of this basic defect in understanding effective therapeutic strategies are lacking for most of them. This in turn results in many children with progressing to end-stage liver disease necessitating orthotopic liver transplantation. Pediatric liver transplants comprise approximately 10% of all liver transplants performed, and the indications for most of them lie among the diseases to be studied in the Childhood Liver Disease Research Network (ChiLDReN). This network combines the efforts of several large and individually successful clinical research enterprises to recruit subjects and carry them through rigorous clinical studies and trials with the expectation of establishing well-characterized patient cohorts that can be followed through the natural history of their disease process and which can be accessed for trials of emerging therapies. In addition, the biological specimens linked to clinical data provide the fuel for studies of etiology (genetic and other) and the influences of gene expression and epigenomics on disease expression and progression, as well as response to therapy. We propose to participate in ChiLDReN as a center wherein investigators have substantial expertise in several of the key areas of investigation within the consortium as a whole. Our center has been one of the top contributors of subjects to every study undertaken by ChiLDReN (and its predecessor consortia) over the term of its existence. We expect to continue to contribute substantially to the performance of ChiLDReN in achieving its goal of successfully eliminating pediatric liver disease as a major cause of infant and childhood morbidity and mortality. The specific aims at our center include: a) to participate fully as a leading clinical center in ChiLDReN; and b) to utilize the currently available specimens from the ChiLDReN biorepository to develop a novel biomarker for fibrosis and determine if activation of the developmental signaling pathway hedgehog contributes to the development of fibrosis in biliary atresia.

描述（由申请人提供）：肝病是婴儿和儿童发病率和死亡率的主要原因。包括“小儿肝病”的疾病是个别罕见的，这阻碍了其原因/病理生理学的研究。由于理解大多数有效的治疗策略的基本缺陷，因此缺乏这种缺陷。反过来，这导致许多患有末期肝病的儿童需要直接肝移植。小儿肝移植物约占进行所有肝移植的10％，大多数肝脏移植物的适应症位于儿童肝病研究网络（儿童）中要研究的疾病。该网络结合了几个大型且单独成功的临床研究企业的努力，以招募受试者，并通过严格的临床研究和试验将其运送，并期望建立良好的患者同类群体，这些患者群体可以通过其疾病过程的自然历史进行遵循，并可以访问新出现疗法的试验。此外，与临床数据相关的生物标本提供了病因学研究（遗传和其他）的燃料，以及基因表达和表观基因组学对疾病表达和进展的影响以及对治疗的反应。我们建议参与儿童作为一个中心，其中调查人员在整个财团内的一些关键调查领域具有丰富的专业知识。我们的中心一直是儿童（及其前任财团）在其存在期间进行的每项研究的最大贡献者之一。我们希望继续为儿童的表现做出基本贡献，以成功消除儿科肝病，这是婴儿和儿童发病率和死亡率的主要原因。针对我们中心的具体目的包括：a）作为儿童领先的临床中心全面参与； b）利用来自儿童生物座的当前可用标本来开发一种新型的纤维化生物标志物，并确定发育信号通路途径刺猬的激活是否有助于胆道闭锁的纤维化发展。