The mechanistic underpinnings of diseases involving the exocrine pancreas are poorly understood. Chronic pancreatitis is often accompanied by inflammation of the pancreas, irreversible fibrosis, and destruction of the pancreatic parenchyma, resulting in abdominal pain, malnutrition, exocrine pancreatic insufficiency, diabetes, and, in some cases, pancreatic cancer. Our Clinical Center (Ohio Kentucky Pancreatitis Research Center (OKPRC)) is interested in continuing our efforts to lead and support the research infrastructure of the Chronic Pancreatitis Clinical Research Consortium to conduct longitudinal clinical research to address the many knowledge gaps related to chronic pancreatitis. 

 

We propose a series of hypothesis-driven studies to: 

1. Validate the use of a novel biomarker for the diagnosis of chronic pancreatitis, 

2. Understand nutritional and metabolic alterations in chronic pancreatitis, and 

3. Advance clinical trials for chronic pancreatitis. 

    

First, we aim to complete a phase 2 (validation) biomarker study of circulating NGAL for the diagnosis of chronic pancreatitis, considering applications to both rule-in and rule-out the disease. In regard to nutritional alterations, we will conduct novel analyses of dietary patterns in participants with chronic pancreatitis to identify associations with disease-related complications and identify potential opportunities for a dietary intervention. We will extend initial analyses regarding the use of a pancreatic hormone (pancreatic polypeptide) as a diagnostic marker of diabetes in the setting of chronic pancreatitis. We will also evaluate for genetic risk in chronic pancreatitis for the development of osteopathy. 

 

Lastly, we describe two clinical trials that are in progress to illustrate the strengths of our collaborative team and opportunities to improve the efficiency of future clinical trials. Altogether, we aim to contribute to the collaborative environment of the Consortium to accomplish these (and other) studies to improve our ability to diagnose and treat chronic pancreatitis.

 

Public Health Relevance Statement

Chronic pancreatitis is associated with inflammation and fibrosis of the pancreas that can lead to sequelae, including abdominal pain, diabetes, exocrine pancreatic insufficiency, osteopathy, and pancreatic cancer. Physicians need accurate tests to better diagnose patients with suspected chronic pancreatitis and identify those with pancreatogenic diabetes before end-organ damage or cancer develops. The Ohio Kentucky Pancreatitis Research Center (OKPRC) will join other Clinical Centers in the Chronic Pancreatitis Clinical Research Consortium (U01) to leverage their collective experience and research infrastructure to further understand how to diagnose and treat chronic pancreatitis and its sequelae.