The objective of this University of Florida/Advent Health proposal within The Chronic Pancreatitis Research Consortium (CPCRC) is to complete recruitment and follow-up of the longitudinal prospective cohort of patients with acute, relapsing acute, and chronic pancreatitis that comprise the PROCEED cohort. The CPCRC is a continuation of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). The major collaborative effort within the CPDPC, and for the CPCRC, is the establishment of a deeply phenotyped cohort with an associated annotated repository of biospecimens (blood, pancreatic and duodenal juice, urine, stool, saliva and when feasible pancreatic tissue), clinical data, and imaging to allow for the identification and validation of biomarkers for risk stratification, early and accurate diagnosis, prognostic modeling, and personalized therapy. 

 

Through the completed acquisition of cohorts of these patients and associated biospecimens, the CPCRC will continue to provide the resources and collaborative opportunities necessary for achieving many of the research objectives identified in the strategic plans of NIDDK- to gain mechanistic insights into the pathophysiology of acute and chronic pancreatitis and develop treatments to prevent or more effectively treat their sequelae- chronic pain, relapse of acute pancreatitis, diabetes, exocrine insufficiency, and the variety of other negative outcomes (metabolic bone disease, sarcopenia, reduced quality of life). 

 

Our proposal addresses several key needs of the CPCRC.

1. A successful platform for recruiting subjects with relapsing acute and chronic pancreatitis, particularly those from subgroups that are inadequately represented in the current PROCEED cohort (Blacks, Hispanics).

2. Completion of two approved and ongoing ancillary studies- one in sarcopenia in relapsing acute and chronic pancreatitis, and one assessing a novel DAMP (eNAMPT) that serves as a master regulator of innate immunity. Sarcopenia is a highly significant clinical issue in patients with pancreatic diseases, and the studies of eNAMPT may lead to novel strategies for clinical trial stratification, and potentially even to therapy as an agent against this molecule is in clinical trials.

3. Mechanistic and pathobiological studies of diabetes across the spectrum of pancreatitis, using archived specimens from cohorts within CPDPC, another UO1 T1DAPC, and the D2d trial (biorepository at AdventHealth). In addition, we propose a novel proof-of-concept trial for pancreatogenic diabetes and a proposal to utilize human pancreatic tissue available at UF and AdventHealth to study the molecular pathology of insulin secretory dysfunction in pancreatitis.

4. To determine the timing, efficacy, and durability of surgical therapy for treating painful chronic pancreatitis in the PROCEED cohort, and to use these findings to establish a clinical trial of surgery across the CPCRC. We believe the types of analyses and studies proposed will be necessary for the work of the CPCRC, and we are able to fully support these aims or related aims selected by the CPCRC.

 

Public Health Relevance Statement

The work of The Chronic Pancreatitis Research Consortium (CPCRC) aims to improve the health and outcomes for patients with acute and chronic pancreatitis. The major collaborative effort for the CPCRC, is the establishment of a deeply phenotyped and longitudinally followed cohort with an associated annotated repository of biospecimens (blood, pancreatic and duodenal juice, urine, stool, saliva and when feasible pancreatic tissue), clinical data, and imaging to allow for the identification and validation of biomarkers for risk stratification, early and accurate diagnosis, prognostic modeling, and personalized therapy. Through the completed acquisition of cohorts of these patients and associated biospecimens, the CPCRC will provide the resources and collaborative opportunities necessary for achieving many of the research objectives identified in the strategic plans of NIDDK- to gain mechanistic insights into the pathophysiology of acute and chronic pancreatitis and develop treatments to prevent or more effectively treat their sequelae- chronic pain, relapse of acute pancreatitis, diabetes, exocrine insufficiency, and the variety of other negative outcomes (metabolic bone disease, sarcopenia, reduced quality of life).