The phase 1/2 trial of indomethacin in chronic pancreatitis (The PAIR trial): Protocol for a parallel multi-center randomized controlled trial

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.