The Phase 1/2 Trial of Indomethacin in Chronic Pancreatitis (The PAIR Trial): Protocol for a Parallel Multi-Center Randomized Controlled Trial

• Authors: Jami L Saloman, University of Pittsburgh; Dhiraj Yadav, University of Pittsburgh; Santhi Swaroop Vege, Mayo Clinic, Rochester, Minnesota; Mark Topazian, University of Washington; Samuel Han, Ohio State University; Darwin L Conwell, University of Kentucky; Liang Li, University of Texas; Alejandra Cervantes, Ohio State University; Phil A Hart, Ohio State University; Zobeida Cruz-Monserrate, Ohio State University; Wenrui Hao, Pennsylvania State University; Gregory Lesinski, Emory University; Thomas Mace, Ohio State University; Tonya M Palermo, University of Washington
• Journal Title: Pancreatology
• Volume: Volume 23, Number 1
• Publisher: Elsevier | 2022-12-15, Pages 42-47
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.pan.2022.12.008
• Subjects: Health Sciences, General; Health Sciences, Medicine and Surgery; Health Sciences, Pharmacology
• Keywords: Chronic Pancreatitis; Indomethacin; Randomized Controlled Trials as Topic; Pain Management; Inflammation

Abstract

Background/Objectives: Current treatments for chronic pancreatitis focus on symptom management and therapeutics targeting disease reversal are lacking. Given the role of the cyclooxygenase-2 (COX-2) enzyme in producing prostaglandin E2 (PGE2), a key component in the inflammatory pathway of chronic pancreatitis, this study evaluates the physiologic effect of oral indomethacin, a COX-2 inhibitor, on PGE2 levels in pancreatic fluid. Methods: This pilot two-center randomized controlled trial seeks to examine 32 subjects with chronic pancreatitis who have no contraindications to indomethacin. Subjects will be randomized to either oral indomethacin 50 mg twice a day or placebo twice a day for a total of 28 days. Baseline (pre-treatment) assessment of pain and quality of life will be performed using the Brief Pain Inventory and the PROMIS-10 questionnaires, respectively. Biological specimens including blood, urine, and saliva will be collected at pre-treatment and post-treatment(day 28). Endoscopic pancreatic function testing with concomitant pancreatic fluid collection will also be performed pre- and post-treatment to assess the change in pancreatic fluid PGE2 levels. The relationship between pancreatic fluid PGE2 levels with blood and saliva PGE2 levels will be examined. Conclusions: This study will elucidate the effect of oral indomethacin on PGE2 levels in the pancreas to assess its role in the inflammatory pathway of chronic pancreatitis. Should indomethacin significantly reduce PGE2 levels, this may represent a potential disease-altering treatment for chronic pancreatitis.