Design: Double-blind, parallel-group, placebo-controlled randomised trial
Population: 107 adults aged 18–60 with painful chronic pancreatitis
Primary outcome: Change in Izbicki pain score at 12 weeks
Effect: Difference −2.5 (95% CI −9.3 to 4.2), P = 0.49

This double-blind, placebo-controlled trial at two academic centres randomised 107 adults aged 18–60 with chronic pancreatitis and chronic abdominal pain — mostly young (mean age 34), male (71%) and idiopathic (66%) — to non-enteric-coated pancreatic enzyme replacement (protease 30,000 U, lipase 25,000 U, amylase 8,000 U per capsule) or placebo for 12 weeks, with follow-up to 24 weeks.

Change in Izbicki pain score at 12 weeks did not differ (between-group difference −2.5, 95% CI −9.3 to 4.2; P = 0.49), and results were similar at 24 weeks. Other secondary outcomes were similar too, apart from the proportion of painful days at 12 weeks, which differed between groups. Adverse events were mild and comparable.

The idea behind non-enteric-coated enzymes is that protease released in the duodenum suppresses cholecystokinin-driven pancreatic stimulation. This trial found no clinical pain benefit. Enzymes should be prescribed for exocrine insufficiency, not as an analgesic strategy.

Do not prescribe non-enteric-coated pancreatic enzymes to treat chronic pancreatitis pain; no enzyme preparation has good evidence as an analgesic.
Continue enteric-coated enzymes with meals where there is exocrine insufficiency.
Manage pain with a structured plan: imaging for obstruction, abstinence, non-opioid analgesia and neuropathic agents.
Refer refractory pain to a pancreatic centre for endoscopic or surgical options.

Why it matters

It removes a widely used but unproven pain strategy from chronic pancreatitis care.

The statistics, in plain English

The difference in pain score was −2.5 points with a confidence interval from −9.3 to 4.2, which crosses zero — no detectable effect. The trial had 107 patients, so a small benefit cannot be excluded, but a meaningful one is unlikely.