Chronic PancreatitisNE-PERTNCT05042284
Effect of Non-enteric Coated Enzymes Substitution on Pain in Patients With Chronic Pancreatitis
A study testing Non-enteric coated pancreatic enzyme preparation in people with Chronic Pancreatitis and Pain, run by Asian Institute of Gastroenterology, India at 1 site in India.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Pancreatitis, Pain
- What is being tested?
- Non-enteric coated pancreatic enzyme preparation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 1 siteIndia
- Study dates
- 1 Sep 2021to 30 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
India1 site
Asian Institute of Gastroenterology
Hyderabad, Andhra Pradesh, 500082
About this study
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)
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.
Read the 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
- Being tested
- Non-enteric coated pancreatic enzyme preparation
- Medical subject headings
- Pancreatitis, Chronic, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-enteric coated pancreatic enzyme preparationDrug
Also called Placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| NE PERT | Experimental | 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) Receives: Drug: Non-enteric coated pancreatic enzyme preparation |
| Placebo | Placebo comparator | Similar appearing glucose capsules will be provided three times a day along with food (breakfast, lunch and dinner) Receives: Drug: Non-enteric coated pancreatic enzyme preparation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in pain score 1
Visual analogue score will be used. Score ranges from 0-10, 10 indicating most severe.
Measured: 3 months
Change in pain score 2
Izbicki pain score will be used. Score ranges from 0-100, 100 indicating most severe.
Measured: 3 months
Secondary outcomes (10)
Change in pain score 1
Visual analogue score will be used. Score ranges from 0-10, 10 indicating most severe.
Measured: 6 months
Change in pain score 2
Izbicki pain score will be used. Score ranges from 0-100, 100 indicating most severe.
Measured: 6 months
Change in number of painful days
Number of days when the patient experienced pain
Measured: 3 months
Change in number of painful days
Number of days when the patient experienced pain
Measured: 6 months
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.
Measured: 3 months
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.
Measured: 6 months
Change in analgesic requirement
Number of analgesic tablets required will be recorded
Measured: 3 months
Change in analgesic requirement
Number of analgesic tablets required will be recorded
Measured: 6 months
Change in the number of hospitalization
Number of hospital admissions and days in hospital will be recorded
Measured: 3 months
Change in the number of hospitalization
Number of hospital admissions and days in hospital will be recorded
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2021
- Study start1 Sep 2021
- Primary completion30 Jul 2024
- Study completion30 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic PancreatitisStudies of the same condition, open and under way.
- More trials run by Asian Institute of Gastroenterology, IndiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asian Institute of Gastroenterology, India
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rupjyoti Talukdar, Asian Institute of Gastroenterology, India
- Investigators
- Rupjyoti Talukdar, MD, AGAF, Principal investigator, Asian Institute of Gastroenterology, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05042284
- Sponsor's protocol ID
- NE PERT 1
- Acronym
- NE-PERT
- Status last verified
- Sep 2024
- First submitted
- 20 Aug 2021
- Last updated
- 4 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Talukdar R, Rasheed A, Unnisa M, Vuyyala C, Goud R, Reddy M, Basha J, Peddapulla C, Tandan M, Reddy ND. Impact of non-enteric-coated pancreatic enzyme replacement therapy (NEPERT) on pain in patients with chronic pancreatitis: a double-blind, parallel-group, placebo-controlled, randomised trial. Gut. 2026 Sep 16:gutjnl-2026-338802. doi: 10.1136/gutjnl-2026-338802. Online ahead of print.
PubMed 42749363
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05042284
- Acronym / sponsor ID
- NE-PERT / NE PERT 1
- Conditions
- Chronic Pancreatitis, Pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Asian Institute of Gastroenterology, IndiaUniversity, hospital or other
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 30 Jul 2024 (actual)
- Study completion
- 30 Jul 2024 (actual)
- First posted
- 13 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NE PERT | Experimental | Drug: Non-enteric coated pancreatic enzyme preparationNon-enteric coated pancreatic enzyme capsules containing 30,000U of protease will be provided three times a day along with food (breakfast, lunch and dinner) |
| Placebo | Placebo comparator | Drug: Non-enteric coated pancreatic enzyme preparationSimilar appearing glucose capsules will be provided three times a day along with food (breakfast, lunch and dinner) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-enteric coated pancreatic enzyme preparationAlso: PlaceboThe patients will be given a non-enteric coated pancreatic enzyme capsule containing 30000 U of protease thrice daily along with meals for 3 months. | Drug | NE PERT, Placebo |
Primary outcome
Change in pain score 1
Time frame: 3 months
Visual analogue score will be used. Score ranges from 0-10, 10 indicating most severe.
Change in pain score 2
Time frame: 3 months
Izbicki pain score will be used. Score ranges from 0-100, 100 indicating most severe.
10 secondary outcomes
Change in pain score 1
Time frame: 6 months
Change in pain score 2
Time frame: 6 months
Change in number of painful days
Time frame: 3 months
Change in number of painful days
Time frame: 6 months
Change in quality of life
Time frame: 3 months
Change in quality of life
Time frame: 6 months
Change in analgesic requirement
Time frame: 3 months
Change in analgesic requirement
Time frame: 6 months
Change in the number of hospitalization
Time frame: 3 months
Change in the number of hospitalization
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Derived from this study: PubMed 42749363Talukdar R, Rasheed A, Unnisa M, Vuyyala C, Goud R, Reddy M, Basha J, Peddapulla C, Tandan M, Reddy ND. Impact of non-enteric-coated pancreatic enzyme replacement therapy (NEPERT) on pain in patients with chronic pancreatitis: a double-blind, parallel-group, placebo-controlled, randomised trial. Gut. 2026 Sep 16:gutjnl-2026-338802. doi: 10.1136/gutjnl-2026-338802. Online ahead of print.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rupjyoti Talukdar, MD, AGAF principal investigator
Asian Institute of Gastroenterology, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Non-enteric coated pancreatic enzyme preparation in people with Chronic Pancreatitis and Pain, run by Asian Institute of Gastroenterology, India at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in pain score 1 (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05042284, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2024.