Continuation of the Childhood Liver Disease Research Network Seattle Clinical Cen

儿童肝病研究网络西雅图临床中心的延续

• 批准号: 8774553
• 负责人: KAREN F MURRAY
• 金额: $ 29.82万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-10 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8774553
• 关键词: Affect; Alagille Syndrome; Alaska; Alaska Native; American; American Indians; Biliary Atresia; Biological; Blood Platelet Disorders; Blood Platelets; Caring; Catchment Area; Child; Child Care; Childhood; Clinical; Collection; Cystic Fibrosis; Data; Databases; Development; Disease; Enrollment; Family; Fibrosis; Functional disorder; Funding; Future; Genetic; Hawaii; Hemorrhage; Hepatology; Idaho; Individual; Investigation; Knowledge; Liver; Liver diseases; Logic; Medical; Metabolic Diseases; Montana; Morbidity - disease rate; Natural History; Operative Surgical Procedures; Oregon; Pacific Northwest; Pathogenesis; Patient Care; Patients; Pediatric Hospitals; Pediatrics; Phenotype; Population; Positioning Attribute; Productivity; Progressive intrahepatic cholestasis; Protein C Inhibitor; Questionnaires; Recruitment Activity; Relative (related person); Research; Risk; Role; Specimen; Syndrome; Techniques; Testing; Thrombelastography; Time; United States; Washington; Wyoming; alpha 1-Antitrypsin Deficiency; base; chronic liver disease; experience; hypercholesterolemia; improved; liver transplantation; mortality; novel; programs; public health relevance; research study

DESCRIPTION (provided by applicant): Biliary atresia and the other childhood cholestatic liver diseases are significant causes of chronic liver disease in children, and the leading causes for liver transplantation in pediatrics. The initial funding periods for the proceeding consortiums leading to Childhood Liver Disease Research Network (ChiLDReN) have resulted in unprecedented collections of well phenotyped subjects and banked data and biological specimens. Although ongoing recruitment of subjects with these rare conditions is needed to allow full attainment of many of the individual study Aims, the collection of subjects, data, and biospecimens is now sufficient to support meaningful investigation into the pathogenesis of these diseases and inform the investigation of novel therapies. This next funding period will continue and expand the currently ongoing research of natural history, genetics, and treatment, by continuing to completion the ongoing studies. Furthermore, new therapies will be trialed in the hopes of improving the care that can be provided to children afflicted with these diseases. Usage of the subject data, biospecimens, and engaged subject populations and their families for advancement of knowledge of these diseases and treatment of affected children will also be a priority for this coming funding period. The Seattle Clinical Center has the experience, expertise, and proven track record to continue participation in ChiLDReN, and has the expected patients over time to support the new consortium trials. Dr. Murray and her Clinical Center team has also proposed a study of bleeding risk and platelet function in Alagille syndrome subjects in comparison to subjects with alpha-1-antitrypsin deficiency and progressive familial intrahepatic cholestasis, that will fill a gap in our knowledge about this condition and significantly impact children with Alagille. This study will use a Pediatric Bleeding Questionnaire to assess bleeding risk in these children, and then analyze their platelet function utilizing the Platelet Functional Analyzer-100 and thromboelastography. The results from analysis of these ChiLDReN subjects will be evaluated in conjunction with collected consortium data on these subjects to verify that children with Alagille syndrome have an increased bleeding risk unique to their syndrome and that this is in part due to platelet dysfunction.

描述（申请人提供）：胆道闭锁和其他儿童胆汁淤积性肝病是儿童慢性肝病的重要原因，也是儿科肝移植的主要原因。正在进行的财团的初始资助期限 儿童肝病研究网络 (ChiLDReN) 的建立，史无前例地收集了表型良好的受试者以及银行数据和生物标本。尽管需要不断招募患有这些罕见疾病的受试者，以充分实现许多单独的研究目标，但受试者、数据和生物样本的收集现在足以支持对这些疾病的发病机制进行有意义的调查，并为以下疾病的调查提供信息：新疗法。下一个资助期将通过继续完成正在进行的研究，继续并扩大目前正在进行的自然历史、遗传学和治疗研究。此外，还将试验新的疗法，希望改善为患有这些疾病的儿童提供的护理。利用受试者数据、生物样本和参与的受试者群体及其家庭来提高对这些疾病的了解和治疗受影响的儿童也将是未来资助期间的优先事项。西雅图临床中心拥有丰富的经验、专业知识、 并拥有继续参与 ChiLDReN 的良好记录，并且随着时间的推移，预计患者将支持新的联合试验。 Murray 博士和她的临床中心团队还提出了一项关于 Alagille 综合征受试者的出血风险和血小板功能的研究，并将其与 α-1-抗胰蛋白酶缺乏症和进行性家族性肝内胆汁淤积症受试者进行比较，这将填补我们对此知识的空白状况并对患有 Alagille 的儿童产生重大影响。本研究将使用儿童出血问卷来评估这些儿童的出血风险，然后利用血小板功能分析仪-100 和血栓弹力图分析他们的血小板功能。对这些 ChiLDReN 受试者的分析结果将与收集到的这些受试者的联合数据一起进行评估，以验证患有 Alagille 综合征的儿童具有其综合征特有的出血风险增加，并且这部分是由于血小板功能障碍所致。