Clinical Center for Cholestatic Liver Disease in Children

儿童胆汁淤积性肝病临床中心

• 批准号: 10414932
• 负责人: Alexander Miethke
• 金额: $ 86.36万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10414932
• 关键词: Acute; Alagille Syndrome; Ancillary Study; Antioxidants; Bile Acids; Biliary; Biliary Atresia; Biological Markers; Caring; Child; Child Care; Childhood; Cholestasis; Clinical; Clinical Data; Clinical Research; Clinical Research Protocols; Clinical Trials; Collection; Cysteine; Cystic Fibrosis; Data; Data Analyses; Data Coordinating Center; Defect; Development; Disease; Disease Outcome; Drainage procedure; Education; Enrollment; Epithelial; Etiology; Funding; Genetic; Goals; Grant; IL8 gene; Infant; Infrastructure; Injury; Institutional Review Boards; Intervention; Intestines; Knowledge; Leadership; Liver; Liver Fibrosis; Liver diseases; Longitudinal Studies; Magnetic Resonance Imaging; Maintenance; Matrilysin; Measures; Mitochondria; Molecular; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal; Observational Study; Outcome; Paper; Pathogenesis; Pathology; Patients; Performance; Portal Hypertension; Positioning Attribute; Progressive intrahepatic cholestasis; Prospective Studies; Protocols documentation; Pruritus; Publications; Quality of life; RNA purification; Radiology Specialty; Reporting; Research; Research Infrastructure; Research Personnel; Role; Safety; Serum; Services; Sodium; Steroids; Time; Tissue Sample; Tissues; Translational Research; U-Series Cooperative Agreements; United States National Institutes of Health; Vancomycin; Work; alpha 1-Antitrypsin Deficiency; base; bile acid transporter; chronic liver disease; clinical center; clinical development; clinical research site; data submission; design; disease natural history; elastography; improved; improved outcome; innovation; intrahepatic; liver cystic fibrosis; liver stiffness; member; open label; primary sclerosing cholangitis; prospective; protocol development; response; small molecule inhibitor; support network; symposium; translational study

PROJECT SUMMARY/ABSTRACT We propose to remain a Member of the Childhood Liver Disease Research Network (ChiLDReN). As a Charter Member of the Network, our proposal represents a logical extension of the long-standing commitment of our Center to improve the care of children with chronic liver disease through innovative patient-based research. In the previous member of the Network, we worked collaboratively with investigators from other Centers and with the Data Coordinating Center to build a strong infrastructure to conduct patient-based studies on biliary atresia, cholestatic syndromes, mitochondrial hepatopathies and cystic fibrosis, with initial work to develop an observational and interventional protocol for children with primary sclerosing cholangitis (PSC). Our key contributions in the previous cycle included: 1) leadership and/or partnership in the development of network-wide clinical studies, with data analyses and publication of 11 original papers; 2) completion of the first two clinical trials (the steroid trial START and the IV-IG trial PRIME); 3) high enrollment and retention of subjects into prospective studies, including the new FORCE study; 4) timely processing of liver tissue by the staff of RNA Purification Service, Bile Acid Analysis Service, and Pathology Service to support Network studies; and 5) co-leading the organization of an NIH symposium on biliary atresia, with publication of its proceedings. We look forward to significantly contributing to the scientific goals and operational excellence of ChiLDReN through three aims. In Aim 1, we will enroll subjects into prospective ChiLDReN protocols to enable observational studies and translational science. This will be done by pursuing high enrollment rate of subjects into approved protocols, with the timely collection and submission of data and tissue samples to meet the enrollment goals established by the Network. In Aim 2, we will develop and implement research protocols for clinical trials. We are working with Network investigators to conduct a trial to determine the efficacy and safety of a small molecule inhibitor of the intestinal sodium-dependent bile acid transporter (IMAGINE-II trial) in children with cholestasis-associated pruritus. We are also developing a clinical trial to determine the efficacy of Vancomycin in children with PSC. And in Aim 3, we propose a new clinical trial focusing on the use of anti- oxidants to decrease biliary injury in infants who acquire biliary drainage after hepatoportoenterostomy for biliary atresia. We also propose an ancillary study to determine the role of matrix metalloproteinase-7 as a biomarker of hepatic fibrosis in biliary atresia. By pursuing the three aims, we will be well positioned to fully execute the new Network aims of pursuing translational science projects and conducting trials to improve the outcome of children with cholestatic liver diseases.

项目总结/摘要 我们建议继续成为儿童肝病研究网络（ChiLDReN）的成员。作为 作为该网络的创始成员，我们的提案代表了长期承诺的逻辑延伸 通过创新的以患者为基础的治疗方法，改善慢性肝病儿童的护理 research.在该网络的前一个成员中，我们与来自其他国家的调查人员合作， 中心和数据协调中心建立强大的基础设施，以开展基于患者的研究 胆道闭锁，胆汁淤积综合征，线粒体肝病和囊性纤维化，初步工作， 为患有原发性硬化性胆管炎（PSC）的儿童制定观察和干预方案。我们 上一个周期的主要贡献包括：（1）在发展中发挥领导作用和/或建立伙伴关系， 全网络临床研究，数据分析和发表11篇原创论文; 2）完成第一个 两项临床试验（类固醇试验START和IV-IG试验PRIME）; 3）高入组率和保留率 受试者进入前瞻性研究，包括新的FORCE研究; 4）及时处理肝脏组织， RNA纯化服务、胆汁酸分析服务和病理学服务的工作人员支持网络 研究;和5）共同领导组织一个关于胆道闭锁的NIH研讨会，并出版其 诉讼我们期待着为实现科学目标和卓越运营做出重大贡献， ChiLDReN通过三个目标。在目标1中，我们将招募受试者进入前瞻性ChiLDReN方案， 观察研究和转化科学。这将通过追求高学科入学率来实现 及时收集和提交数据和组织样本，以满足 网络所设定的目标。在目标2中，我们将制定和实施研究协议， 临床试验我们正在与网络调查人员合作进行试验，以确定疗效和安全性 肠钠依赖性胆汁酸转运蛋白的小分子抑制剂（IMAGINE-II试验） 患有胆汁淤积相关瘙痒症的儿童。我们还在开展一项临床试验，以确定 万古霉素治疗PSC儿童在目标3中，我们提出了一项新的临床试验，重点是使用抗- 氧化剂减少肝门肠吻合术后胆道引流的婴儿的胆道损伤 胆道闭锁我们还提出了一项辅助研究，以确定基质金属蛋白酶-7的作用， 胆道闭锁患者肝纤维化的生物标志物。通过实现这三个目标，我们将处于有利地位， 执行新的网络目标，追求转化科学项目，并进行试验，以改善 儿童胆汁淤积性肝病的预后