Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas leading to fibrosis and organ dysfunction. Clinical features of CP are highly variable and include minimal or no symptoms to debilitating pain, episode(s) of acute pancreatitis (AP), exocrine and/or endocrine insufficiency (Type 3c diabetes mellitus; T3cDM), local and/or systemic complications and pancreatic ductal adenocarcinoma (PDAC). The consortium for the study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC) was formed in 2015 (U01DK108323) to undertake comprehensive clinical, epidemiological, and biological characterization of patients with CP to gain insight into the pathophysiology of CP and its sequelae. CPDPC investigators are conducting well-powered studies of risk factors, environmental influences, and proof-of-concept studies to move the field forward, particularly those factors that increase the risk of T3cDM and PDAC. Four high-priority studies have been proposed to meet the goals and specific aims (SA) of the CPDPC. SA#1: The PROCEED study is a prospective, observational, longitudinal cohort study of the natural history of CP. The primary hypothesis of PROCEED is that prospective ascertainment and follow-up of a well-phenotyped cohort of subjects at different stages of CP will accurately define its natural history and associated complications. SA#2. New onset diabetes (NoD) in patients age 50 years or older may be an early manifestation of PDAC. The NoD study will define, identify and follow a large cohort of these high-risk subjects with NoD for the development of PDAC. SA#3: The DETECT study will use a mixed meal test to further our understanding of islet dysfunction and the different pathophysiologic mechanisms in type 2 diabetes and T3cDM. SA#4: The INSPPIRE 2 study, a multicenter, multidisciplinary collaboration to examine pediatric pancreatitis, aims to build a large, well-characterized, diverse prospective cohort of children with recurrent AP or CP. The size and scope of this cohort will provide data to significantly deepen our understanding of the pathogenesis and progression for these diseases and a framework for studying interventions to slow or reverse disease progression. All four studies will also contribute to a biorepository, providing a framework to develop biomarkers of early diagnosis and prediction of disease progression, understand disease mechanisms, and discover genetic factors affecting susceptibility and progression. We anticipate that the investigations proposed will achieve goals never attempted in the study of CP.

Public Health Relevance

Chronic pancreatitis is a progressive, unrelenting disease, often leading to loss of exocrine and endocrine function and debilitating abdominal pain, resulting in significant healthcare costs. It is unknown why some individuals progress to severe disease and develop serious complications, including diabetes and/or pancreas cancer. Investigators from Indiana University, as part of the consortium for the study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC), are collaborating with investigators from other consortium sites to conduct well-powered studies of risk factors, environmental influences, and proof-of-concept studies to move the field forward, particularly those factors that increase the risk of diabetes and malignancy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK108323-04S1
Application #
9751583
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Unalp-Arida, Aynur
Project Start
2015-09-28
Project End
2020-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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