Effect of Non-enteric Coated Enzymes Substitution on Pain in Patients With Chronic Pancreatitis
Status:
Not yet recruiting
Trial end date:
2022-12-31
Target enrollment:
Participant gender:
Summary
Pain in CP entails several independent yet overlapping mechanisms including oxidative
stress-mediated parenchymal inflammation, pancreatic and central neuropathy and
neuroplasticity. Medical modalities for long-term pain management includes antioxidants and
neuromodulators. Pancreatic enzymes are also invariably used for pain management. CP with
ductal obstruction and pain is treated with either endotherapy or drainage surgery. However,
it has been observed that a substantially increasing proportion of patients experience pain
recurrence as the duration of follow-up after endotherapy or surgery gets longer.
Neural and dietary (proteins) stimuli activate CCK receptors in D1 & D2 which gives a
positive feedback signal for pancreatic secretion. Once enzyme secretion starts, due to
ductal and interstitial/tissue hypertension, nociception begins that results in pain.
Blockade of the duodenal CCK receptors could inhibit the positive feedback loop, thereby
reducing pancreatic secretion and resulting pain. Currently available enteric coated enzyme
supplements are released throughout the small bowel and therefore may not be released
sufficiently in the duodenum to effectively suppress the feedback loops. High doses of
proteases (~25k-30k) would be required to block the receptors, while most of the currently
available preparations have higher lipase but not proteases.
This led to the investigators' hypothesis that negative feedback of CCK by non enteric coated
pancreatic enzymes could ameliorate pain in a more effective manner by NE-PERT.