Effect of Non-enteric Coated Enzymes Substitution on Pain in Patients With Chronic Pancreatitis (NE-PERT)

A

Asian Institute of Gastroenterology, India

Status

Enrolling

Conditions

Chronic Pancreatitis
Pain

Treatments

Drug: Non-enteric coated pancreatic enzyme preparation

Study type

Interventional

Funder types

Other

Identifiers

NCT05042284
NE PERT 1

Details and patient eligibility

About

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.

Full description

Chronic pancreatitis (CP) is a fibro-inflammatory disorder of the pancreas characterized by progressive and irreversible damage. It manifests with abdominal pain and/or exocrine or endocrine insufficiency. Recurrent abdominal pain is the dominant clinical hallmark that mandates aggressive management. 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. It has been postulated that neural and dietary (proteins) stimuli activate CCK receptors in D1 & D2 which gives a positive feedback signal for pancreatic secretion. Once enzyme secretion from the pancreas begins, due to ductal and interstitial/tissue hypertension, nociception is initiated that results in pain. On this premise, the investigators hypothesized that blocking the duodenal CCK receptors could inhibit the positive feedback loop, thereby reducing pancreatic secretion and resulting pain. Earlier meta-analyses that evaluated the effect of pancreatic enzyme supplementation on pain reported that there were no overall benefits in pain management. All but two of those studies used enteric coated enzyme. 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. However, on subgroup analyses in the aforementioned meta-analyses, pain reduction was observed in the two studies that used non-enteric coated preparations. These studies were done several years earlier, had a small sample size, and had a cross over design. This formed that rationale of the investigators' current study to test the hypothesis using a statistically valid design with a higher sample size that would allow subgroup analyses, adjust for alternative pain mechanisms, and achieve a better effect size.

Enrollment

76 estimated patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Chronic pancreatitis of at least 3 years
  • At least 3 episodes of pain in the past 3 months
  • Pain score of at least 3 on VAS (0-10)
  • Age 18-60yrs
  • Both genders

Exclusion criteria

  • Acute pancreatitis episode at the time of enrolment.
  • Pancreatic cancer.
  • Other chronic painful conditions.
  • Active substance use (alcohol, smoking, smokeless tobacco, illicit drugs).
  • Pregnancy and lactation.
  • Inability to give informed consent.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

76 participants in 2 patient groups, including a placebo group

NE PERT
Experimental group
Description:
Non-enteric coated pancreatic enzyme capsules containing 30,000U of protease will be provided three times a day along with food (breakfast, lunch and dinner)
Treatment:
Drug: Non-enteric coated pancreatic enzyme preparation
Placebo
Placebo Comparator group
Description:
Similar appearing glucose capsules will be provided three times a day along with food (breakfast, lunch and dinner)
Treatment:
Drug: Non-enteric coated pancreatic enzyme preparation

Trial contacts and locations

0

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Central trial contact

Rupjyoti Talukdar, MD, AGAF

Data sourced from clinicaltrials.gov

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