Public Health Statement

Chronic pancreatitis (CP) is an emerging, but poorly understood condition in children that significantly impacts quality of life with high healthcare costs. The objective of this application is to delineate the natural history of pediatric CP through careful longitudinal analysis of the INSPPIRE-2 cohort, to identify diagnostic and prognostic non-invasive biomarkers involved in disease progression, and to improve pain and health related quality of life through innovative clinical trials.

Project Abstract

Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are rare, but highly burdensome diseases without a cure. ARP progresses to CP complicated by pain, exocrine pancreatic insufficiency (EPI), and diabetes mellitus (DM). 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.

Most of our current understanding comes from INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE, PIs: Aliye Uc and Mark Lowe), the first and largest multicenter, multidisciplinary collaboration to carefully phenotype children with ARP and CP, collect longitudinal data and create a network of pediatric centers ready to perform clinical trials.

Through INSPPIRE, we have determined for the first time that, contrary to adults with environmental risk factors, genetic or anatomic factors drive the disease in children, with frequent abdominal pain, hospitalizations, emergency room visits missed school days, surgical and endoscopic interventions, costing significant burden to children, families and US health care. Despite this progress, no effective interventions to prevent end-organ failure and complications of CP exist because gaps remain in understanding the determinants and biomarkers for disease progression in pediatric CP.

This competitive renewal application is responsive to the objectives of the U01 RFA DK-25-019 to define the profiles of disease progression in pediatric CP through careful longitudinal analysis of the INSPPIRE-2 cohort including innovative approaches to prospectively follow children with ARP and CP into adulthood, to identify diagnostic and prognostic non-invasive biomarkers involved in disease progression, to propose clinical trials to address the underlying causes, improve pain and health related quality of life (HRQOL) and to evaluate treatment response.

Our specific aims are:

• Aim 1.) Define the natural history of pediatric ARP and CP and identify variables that drive outcomes.

• Aim 2.) Develop non- invasive biomarkers of disease progression in pediatric CP.

• Aim 3.) Improve outcomes of childhood CP by addressing drivers of progression.

This renewal application will define the natural history of pediatric CP, investigate the impact of risk factors on disease course, study non-invasive biomarkers on disease development and propose two innovative clinical trials of drug repurposing based on novel and exciting preliminary data.

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