A Randomized, Double-Blind, Non-Inferiority Trial Comparing Microbial and Porcine Pancreatic Enzyme Replacement Therapy in Chronic Pancreatitis (Np-Pert Trial) - Protocol

Background Chronic pancreatitis (CP) is a progressive inflammatory disorder causing irreversible pancreatic damage, eventually resulting in pancreatic exocrine insufficiency (PEI). This may lead to malabsorption, malnutrition, weight loss, and impaired quality of life. Pancreatic enzyme replacement therapy (PERT) is the standard treatment for PEI and is predominantly derived from porcine sources. However, religious, ethical, dietary, and supply-related concerns highlight the need for effective non-porcine alternatives. Microbial based pancreatic enzymes have shown promising safety and efficacy in preliminary studies, but evidence in CP remains limited. Objective To compare the efficacy and safety of non-porcine microbial -based pancreatin with standard porcine-based pancreatin in patients with PEI secondary to CP. Methods This investigator-initiated, randomized, double-blind, single-center, non-inferiority trial will enroll 134 adults with CP-associated PEI (defined as having a faecal elastase < 100 µg/g) and a Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) score of > 1.4. After a two-week washout period, participants will be randomized 1:1 to receive either microbial-based or porcine-based pancreatin for 12 weeks. The primary outcome is the change from baseline in the PEI-Q score at 12 weeks. Secondary outcomes include nutritional status, anthropometric measures, gastrointestinal symptoms, pain scores, stool consistency, glycemic parameters, laboratory markers, and quality of life. Discussion This study aims to evaluate whether microbial-based pancreatin is non-inferior to porcine-based therapy and may provide a culturally acceptable and sustainable alternative for managing CP-related PEI.