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

Pain Clinical Trial

— NE-PERT  

Official title:

Effect of Non-enteric Coated Enzymes Substitution on Pain in Patients With Chronic Pancreatitis: a Double -Blinded Placebo Controlled Randomized Trial (NE-PERT Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05042284
• Other study ID #: NE PERT 1
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2021
• Est. completion date: July 30, 2024

Study information

• Verified date: February 2024
• Source: Asian Institute of Gastroenterology, India
• Contact: Rupjyoti Talukdar, MD, AGAF
• Phone: 7032804213
• Email: rup_talukdar[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: July 30, 2024
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Pancreatitis
• Pain
• Pancreatitis
• Pancreatitis, Chronic

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
India	Asian Institute of Gastroenterology	Hyderabad	Andhra Pradesh

Sponsors (1)

Lead Sponsor	Collaborator
Asian Institute of Gastroenterology, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Quantitative sensory testing parameters (pin prick) [First follow-up]	Pin prick sensation (0-10; 10 indicates maximum)	3 months
Other	Change in Quantitative sensory testing parameters (pin prick) [Second follow-up]	Pin prick sensation (0-10; 10 indicates maximum);	6 months
Other	Change in Quantitative sensory testing parameters (cold tolerance) [First follow-up]	Cold tolerance (0-10 VAS every 10secs for 2 mins.; 10 indicates severe)	3 months
Other	Change in Quantitative sensory testing parameters (cold tolerance) [Second follow-up]	Cold tolerance (0-10 VAS every 10secs for 2 mins.; 10 indicates severe)	6 months
Other	Change in pain DETECT score [First follow-up]	The painDETECT questionnaire will be used. Range is 0-38, 38 indicates most severe neuropathic pain.	3 months
Other	Change in pain DETECT score [Second follow-up]	The painDETECT questionnaire will be used. Range is 0-38, 38 indicates most severe neuropathic pain.	6 months
Primary	Change in pain score	IZBICKI pain score will be used. Score ranges from 0-100, 100 indicating most severe.	3 months
Primary	Change in pain score	IZBICKI pain score will be used. Score ranges from 0-100, 100 indicating most severe.	6 months
Secondary	Change in number of painful days	Number of days when the patient experienced pain	3 months
Secondary	Change in number of painful days	Number of days when the patient experienced pain	6 months
Secondary	Change in quality of life	Will be measured using the EORTC QLQ c30 with PAN28 tool. Score ranges from 0 to 100. 0 indicates worst for function scales, while 100 indicates worst for symptom scales.	3 months
Secondary	Change in quality of life	Will be measured using the EORTC QLQ c30 with PAN28 tool. Score ranges from 0 to 100. 0 indicates worst for function scales, while 100 indicates worst for symptom scales.	6 months
Secondary	Change in analgesic requirement	Number of analgesic tablets required will be recorded	3 months
Secondary	Change in analgesic requirement	Number of analgesic tablets required will be recorded	6 months
Secondary	Change in the number of hospitalization	Number of hospital admissions and days in hospital will be recorded	3 months
Secondary	Change in the number of hospitalization	Number of hospital admissions and days in hospital will be recorded	6 months