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

吲哚美辛治疗慢性胰腺炎的 I/II 期临床试验(PAIR 试验):一项平行多中心随机对照试验方案

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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 E(2) (PGE(2)), a key component in the inflammatory pathway of chronic pancreatitis, this study evaluates the physiologic effect of oral indomethacin, a COX-2 inhibitor, on PGE(2) 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 PGE(2) levels. The relationship between pancreatic fluid PGE(2) levels with blood and saliva PGE(2) levels will be examined. CONCLUSIONS: This study will elucidate the effect of oral indomethacin on PGE(2) levels in the pancreas to assess its role in the inflammatory pathway of chronic pancreatitis. Should indomethacin significantly reduce PGE(2) levels, this may represent a potential disease-altering treatment for chronic pancreatitis.

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