INSPPIRE: A Longitudinal Cohort Study of Pediatric Chronic Pancreatitis to Predict Clinical Course and Identify Disease Modifiers

INSPPIRE：儿科慢性胰腺炎的纵向队列研究，用于预测临床病程并确定疾病调节因子

• 批准号: 10252050
• 负责人: MARK E. LOWE
• 金额: $ 46.3万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-28 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10252050
• 关键词: Acute; Adult; Age; Aggressive course; Ancillary Study; Autoantibodies; Autoimmunity; Beta Cell; C-Peptide; Characteristics; Child; Childhood; Clinical; Cognitive Therapy; Cohort Analysis; Cystic Fibrosis Transmembrane Conductance Regulator; Defect; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Disease Progression; Endocrine; Environmental Risk Factor; Exocrine pancreatic insufficiency; Fibrosis; Functional disorder; Funding; Genes; Genetic; Genetic Risk; Genetic Screening; Glucagon; Glucose; Goals; Health Care Costs; Hyperlipidemia; Hypertriglyceridemia; Image; Impaired health; Incidence; Insulin; Interdisciplinary Study; International; Islet Cell; Longitudinal cohort study; Modality; Natural History; Onset of illness; Outcome; Pain; Pancreatic Polypeptide; Pancreatitis; Pathogenicity; Patient Outcomes Assessments; Pediatric cohort; Peptides; Physiologic calcification; Prediabetes syndrome; Predisposing Factor; Prevalence; Prognostic Factor; Quality of life; Recurrence; Research Personnel; Risk; Risk Factors; SPINK1 gene; Susceptibility Gene; Testing; Therapeutic; United States National Institutes of Health; Variant; Work; acute pancreatitis; blood glucose regulation; burden of illness; chronic pancreatitis; clinical predictors; cohort; demographics; disability; early onset; genetic risk factor; genetic variant; genomic locus; glucagon-like peptide 1; glucose tolerance; health related quality of life; innovation; insight; islet; longitudinal analysis; premature; prospective; response; risk variant

PROJECT SUMMARY Acute pancreatitis (AP) is increasingly recognized in children, with an incidence approaching that of adults. Most children with pancreatitis have a single, mild, acute episode that resolves without complications. However, a subset of children with AP develops recurrent episodes (defined as acute recurrent pancreatitis or ARP) and some progress to chronic pancreatitis (CP). Pediatric ARP and CP significantly impact quality of life and carry high healthcare costs. Few studies have been performed to characterize the natural history pediatric ARP and CP, to identify its risk factors and to determine predictors of disease course. As INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE), the first multicenter, multidisciplinary collaboration in pediatric pancreatitis, we determined that children with ARP harbor multiple genetic risk variants and rapidly transition to CP, exocrine pancreatic insufficiency (EPI) and diabetes mellitus (DM). The risk factors that predispose children to early onset pancreatitis, rapid progression to CP and premature loss of exocrine and endocrine function are not well-known. The objective of this application is to delineate the natural history of pediatric CP through careful prospective analysis of INSPPIRE-2 cohort, to define the impact of genetic modifiers on disease course and to determine the mechanisms involved in pancreatogenic diabetes mellitus (T3cDM). The overall hypothesis is that genetic factors predispose children to early onset CP, EPI, and DM. Our specific aims are: 1) Characterize pediatric CP, determine predictors of disease onset and progression; 2) Determine the impact of genetic variants on disease onset and progression; 3) Identify mechanisms underlying disturbed glucose regulation in pediatric ARP and CP. This project will provide insight into the pathophysiology of pediatric pancreatitis, investigate the impact of genetic variants on disease course and explore the mechanisms of early islet cell dysfunction in pediatric ARP and CP. Our long-term goal is to develop diagnostic modalities, prognostic factors and innovative treatment approaches for pediatric ARP and CP.

项目总结