Chronic pancreatitis (CP) is a progressive disease, often leading to loss of exocrine and endocrine function and debilitating abdominal pain. It is unknown why some individuals progress and develop complications, including pancreatogenic diabetes (T3cDM) and/or pancreatic cancer (PDAC). In this Consortium, investigators have proposed and initiated several well-powered studies of risk factors, environmental influences, and proof-of-concept studies to move the field forward. While two cohort studies are ongoing (PROCEED and INSPPIRE-2), we offer new innovative proposals to address other research objectives identified by the NIDDK. 

 

We propose several specific aims (SA) to meet the goals of RFA-DK-25-019.:

1. We propose to continue the CPDPC’s two main longitudinal studies: PROCEED, INSPPIRE 2.

2. We offer a proposal that builds upon the success of our ancillary study, MINIMAP, completed during the last funding cycle. We will validate MRI and novel criteria as biomarkers for the diagnosis of and progression to CP using the PROCEED cohort.

3. Galectin-3 (Gal-3) is a carbohydrate-binding protein that appears to be involved in fibrogenesis and tissue remodeling in CP. A Gal-3 inhibitor is safe and shows potential for reducing hepatic fibrosis in non-alcoholic steatohepatitis. We propose to test the hypothesis that a Gal-3 inhibitor is safe and efficacious in patients with CP and may reverse or halt the fibrosis observed in CP. We will evaluate changes in pancreatic fibrosis as assessed by MRI, as well as serum and pancreatic fluid exploratory biomarkers.

4. We propose innovative studies evaluating different strategies and interventions focused on alleviating abdominal pain in CP patients. Lacosamide, an anti-epileptic drug, appears to inhibit opioid-induced hyperalgesia.

   1. We will perform a phase-2 double-blind placebo-controlled trial evaluating the efficacy of adding lacosamide to opioid therapy for change in pain control, opioid use, and quality of life for patients with painful CP.

   2. Quantitative sensory testing (QST) uses electrical and pressure stimulation at different dermatomes to unravel the pain system. Endoscopic ultrasound (EUS) with celiac plexus block can be an effective intervention for alleviating pain attributable to CP. We will investigate:

      1. QST profiles, demographic and clinical characteristics in patients with painful CP referred for EUS celiac plexus block;

      2. Whether the QST profile can be used to predict the clinical outcome of EUS celiac plexus block.

 

Public Health Relevance Statement

Chronic pancreatitis (CP) is a progressive, unrelenting disease, often leading to loss of exocrine and endocrine function and debilitating abdominal pain, resulting in significant healthcare costs. The Consortium for the study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC), formed in 2015, has been tasked with undertaking comprehensive clinical, epidemiological, and biological characterization of patients with CP (including adults and children with acute recurrent pancreatitis) to develop treatments and gain insight into the pathophysiology of CP and its sequela: chronic pain, pancreatic exocrine and endocrine insufficiency, and the diabetes/pancreatic cancer association. The Indiana University clinical center pledges to continue its contribution to ongoing studies by participating in the Chronic Pancreatitis Clinical Research Consortium (CPCRC), and proposes additional ancillary studies, which will be described herein.