Effect of Non-enteric Coated Enzymes Substitution on Pain in Patients With Chronic Pancreatitis

NCT ID: NCT05042284

Last Updated: 2024-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2024-07-30

Brief 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.

Detailed 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.

Conditions

Chronic Pancreatitis; Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NE PERT

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)

Group Type: EXPERIMENTAL

Non-enteric coated pancreatic enzyme preparation

Intervention Type: DRUG

The patients will be given a non-enteric coated pancreatic enzyme capsule containing 30000 U of protease thrice daily along with meals for 3 months.

Placebo

Similar appearing glucose capsules will be provided three times a day along with food (breakfast, lunch and dinner)

Group Type: PLACEBO_COMPARATOR

Non-enteric coated pancreatic enzyme preparation

Intervention Type: DRUG

The patients will be given a non-enteric coated pancreatic enzyme capsule containing 30000 U of protease thrice daily along with meals for 3 months.

Interventions

Non-enteric coated pancreatic enzyme preparation

The patients will be given a non-enteric coated pancreatic enzyme capsule containing 30000 U of protease thrice daily along with meals for 3 months.

Intervention Type: DRUG

Other Intervention Names

Placebo

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asian Institute of Gastroenterology, India

OTHER

Sponsor Role: lead

Responsible Party

Rupjyoti Talukdar

Director, Pancreatology; Head, Pancreas Research Group and Division of Gut Microbiome Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rupjyoti Talukdar, MD, AGAF

Role: PRINCIPAL_INVESTIGATOR

Asian Institute of Gastroenterology

Locations

Asian Institute of Gastroenterology

Hyderabad, Andhra Pradesh, India

Countries

India

Other Identifiers

NE PERT 1

Identifier Type: -

Identifier Source: org_study_id