Personalized Education and Pain Response in Chronic Pancreatitis (PEPCP)

Impact of Personalized Education on Pain Response in Patients With Chronic Pancreatitis (PEPCP)

Pain mechanisms in chronic pancreatitis (CP) are heterogeneous and includes nociception, pancreatic neuropathy and central neuropathy/neuroplasty. These mechanisms could occur simultaneously in variable proportions and could explain why several patients develop recurrence of pain even after being treated by all the currently available modalities, such as antioxidants, endoscopic therapies and surgery.

In the studies by the investigators over the past 2 years, they observed that persistent pain in these patients was associated with varying grades of depression and poor quality of life. This was accompanied by alteration in the metabolites in the brain (anterior cingulate cortex, prefrontal cortex, hippocampus, and basal ganglia) as evidenced in magnetic resonance spectroscopy (MRS) of the brain. These areas in the brain are responsible for pain modulation, long-term pain memory and emotional responses to pain.

When the investigators counselled these patients and explained their disease and possible outcomes based on their own clinical course, imaging and treatment response (personalized education/counselling), they reported significant improvement in depression, quality of life parameters and, interestingly, also in pain. Further, there were changes in the metabolite parameters in the brain on MRS after personalized counselling/education that was more similar to that of healthy controls.

This led to our hypothesis that better understanding of the disease and its outcomes by the patients could improve their coping capabilities and increase their pain thresholds. This could augment the pain responses of these patients to the other therapeutic modalities.

We will conduct this single blinded, placebo controlled, randomized controlled trial on patients with documented CP of over 3 years duration, who had at least 3 episodes of abdominal pain of over the past 3 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Pancreatitis; Depression, Anxiety; Pain Syndrome
• Intervention / Treatment: Other: Personalised education

Detailed Description

Chronic pancreatitis (CP) is characterised by pain, exocrine insufficiency and endocrine dysfunction. Of all symptoms, intractable abdominal pain is the most debilitating that mandates a multidisciplinary treatment approach. Long term treatment of pain begins with antioxidants. If the pancreatic duct contains stones in a limited area (head, neck and proximal body), the patient is subjected to endoscopic treatment, which includes extracorporeal shock wave lithotripsy (ESWL) for large stones (>5mm) with or without pancreatic duct stenting. For smaller stones, endoscopic retrograde cholangiopancreatography (ERCP) alone suffices. ERCP with pancreatic ductal stenting is also the first line treatment for a solitary symptomatic pancreatic ductal stricture. If symptomatic stones are located all along the pancreatic duct, or if there are multiple strictures, surgical drainage of the pancreatic duct becomes the treatment of choice. If there are any mass lesion in the pancreas on the background of CP, then resection procedures such as Whipple's operation or distal pancreatectomy with/without splenectomy is resorted to.

Even though the above mentioned modalities are directed to relief the patient of pain, a substantial proportion of patients return with recurrence of pain. This explains the complexity in the pain mechanisms in CP. Pain mechanisms in chronic pancreatitis (CP) are heterogeneous and includes nociception, pancreatic neuropathy and central neuropathy/neuroplasticity. These mechanisms could occur simultaneously in variable proportions and could explain why several patients develop recurrence of pain even after being treated by all the currently available modalities.

Since CP is a chronic disease with systemic effects, several additional factors could impact the evolution and response to pain. These could include the patient's personality traits, educational background, family history of CP, previous experience of the disease, background knowledge of CP, coping capability, to name a few. The investigators have been working on these aspects for the past couple of years, wherein they looked into the mental status (depression/anxiety), quality of life and the impact of pain in these aspects. Since pain memory and emotional responses to pain is mediated by the basal ganglia, hippocampus, anterior cingulate cortex and prefrontal cortex of the brain, the investigators also looked at the metabolites in these areas using magnetic resonance spectroscopy. The investigators observed that persistent pain in these patients will be associated with varying grades of depression and poor quality of life. This was accompanied by alteration in the metabolites myoinositol, creatine, glycine/glutamate in the hippocampus, and basal ganglia Following this, when the investigators counselled these patients and explained their disease and possible outcomes based on their own clinical course, imaging and treatment response (personalized education/counselling), they reported significant improvement in depression, quality of life parameters and, interestingly, also in pain. Further, there were changes in the metabolite parameters in the brain on MRS after personalized counselling/education that were more closer to that of healthy controls.

This led to the hypothesis that better understanding of the disease and its outcomes by the patients could improve their coping capabilities and increase their pain thresholds. This could augment the pain responses of these patients to the other therapeutic modalities.

The investigators will conduct this single blinded, placebo controlled, randomized controlled trial on patients with documented CP of over 3 years duration, who had at least 3 episodes of abdominal pain of over the past 3 months.

The investigators will provide detailed education regarding the disease to the patients (based on their disease characteristics) in the study arm and evaluate the changes in pain scores, pain episodes, QOL, mental status and metabolomic status in the brain (hippocampus, basal ganglia, anterior cingulate cortex, prefrontal cortex).

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rupjyoti Talukdar, MD, FICP, AGAF; Phone Number: 7032804231; Email: rup_talukdar@yahoo.com

Study Locations

• India
  • Telangana
    • Hyderabad, Telangana, India, 500032
      • Asian Institute of Gastroenterology
      • Contact: Rupjyoti Talukdar, MD, FICP, AGAF, FRCP, FRSB; Phone Number: +917032804231; Email: rup_talukdar@yahoo.com
      • Contact: Shagufta Farheen, Pharm D; Email: shagufta12farheen@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Chronic pancreatitis of at least 3 years
• At least 3 episodes of pain in the past 3 months
• Age 18-60yrs
• Both genders

Exclusion Criteria:

• Acute pancreatitis episode at the time of enrolment.
• Pancreatic cancer.
• Other chronic diseases (including end organ damage related to diabetes).
• Adverse life event in the family in the past 6 months.
• Active substance use (alcohol, smoking, smokeless tobacco, Illicit drugs).
• Pregnancy and lactation.
• Psychiatric illness at enrolment or during follow-up, and/or concomitant intake of antidepressants and neuromodulators..

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalised education; Greetings.; Recording of demographic, clinical (disease related), nutritional, laboratory, and treatment related data.; Administration of questionnaires.; Inquiring patient's perception of their disease.; Explaining the patient about their disease in general followed by specific aspects and possible outcomes in the context of their perception, clinical aspects, questionnaire, and imaging data. In addition, the general treatment plan will be explained.; Address all queries from the patient and care givers.	Other: Personalised education; Patients will be explained about their disease and possible outcomes based on clinical, biochemical and imaging data.
No Intervention: Standard communication; Greetings.; Recording of demographic, clinical (disease related), nutritional, laboratory, imaging and treatment related data.; Administration of questionnaires.; Explaining the general treatment plan.; Address general treatment related queries from the patient and care givers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain score	Pain will be measured using the Visual analog scale (0-10)	3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of painful days	The patient will record the number of painful days in a self reported pain questionnaire.	3 and 6 months
Change in neuropathic pain	Neuropathic pain will be evaluated using the PainDetect tool	3 and 6 months
Change in quality of life (QOL)	Quality of life (QOL) will be measured using the EORTC QLQ 30	3 and 6 months
Change in depression score	Depression will be measured using Beck depression Inventory (BDI) II	3 and 6 months
Change in depression score	Depression will be measured using Hospital Anxiety and Depression Score (HADS).	3 and 6 months
Change in multidimensional aspects of pain	Multidimensional aspects of pain will be measured using the COMPAT-SF	3 and 6 months
Change in the psychological aspects of pain	Psychological aspects of pain will be measured using the Pain Catastrophising score (PCS)	3 and 6 months
Change in the patient's perception of alteration in pain	Patient's perception of alteration in pain will be measured using the Patient's Global Impression of Pain (PGIC)	3 and 6 months
Difference in analgesic requirement	Difference in analgesic requirement will be measured by number of opioids and NSAIDs requirement	3 and 6 months
Change in the number of hospital visits	The patient will record the number of hospital visits in a self reported daily questionnaire.	3 and 6 months
Change in anxiety score	Anxiety will be measured using the Hospital anxiety and depression (HADS) tools.	3 and 6 months
Change in sleep behaviour	Change in sleep behaviour will be measured using the Pittsburg Sleep Quality Index	3 and 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of possible mechanisms of improvement.	Possible mechanisms of improvement improvement will be assessed by measuring the plasma metabolites serotonin, dopamine, oxytocin, GABA, tryptophan and endorphins.	3 and 6 months

Collaborators and Investigators

• Sponsor: Asian Institute of Gastroenterology, India
• Investigators: Principal Investigator: Rupjyoti Talukdar, MD, FICP, AGAF, Asian Institute of Gastroenterology

Publications and helpful links

General Publications

• Olesen SS, Bouwense SA, Wilder-Smith OH, van Goor H, Drewes AM. Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial. Gastroenterology. 2011 Aug;141(2):536-43. doi: 10.1053/j.gastro.2011.04.003. Epub 2011 Apr 14.
• Bloechle C, Izbicki JR, Knoefel WT, Kuechler T, Broelsch CE. Quality of life in chronic pancreatitis--results after duodenum-preserving resection of the head of the pancreas. Pancreas. 1995 Jul;11(1):77-85. doi: 10.1097/00006676-199507000-00008.
• Talukdar R, Reddy DN. Pain in chronic pancreatitis: managing beyond the pancreatic duct. World J Gastroenterol. 2013 Oct 14;19(38):6319-28. doi: 10.3748/wjg.v19.i38.6319.
• Talukdar R, Nageshwar Reddy D. Is there a single therapeutic target for chronic pancreatitis pain? Gastroenterology. 2013 Mar;144(3):e18. doi: 10.1053/j.gastro.2012.12.033. Epub 2013 Jan 25. No abstract available.
• Dimcevski G, Sami SA, Funch-Jensen P, Le Pera D, Valeriani M, Arendt-Nielsen L, Drewes AM. Pain in chronic pancreatitis: the role of reorganization in the central nervous system. Gastroenterology. 2007 Apr;132(4):1546-56. doi: 10.1053/j.gastro.2007.01.037. Epub 2007 Jan 25.
• Ceyhan GO, Demir IE, Rauch U, Bergmann F, Muller MW, Buchler MW, Friess H, Schafer KH. Pancreatic neuropathy results in "neural remodeling" and altered pancreatic innervation in chronic pancreatitis and pancreatic cancer. Am J Gastroenterol. 2009 Oct;104(10):2555-65. doi: 10.1038/ajg.2009.380. Epub 2009 Jun 30.
• Nguyen-Tang T, Dumonceau JM. Endoscopic treatment in chronic pancreatitis, timing, duration and type of intervention. Best Pract Res Clin Gastroenterol. 2010 Jun;24(3):281-98. doi: 10.1016/j.bpg.2010.03.002.
• Talukdar R, Murthy HV, Reddy DN. Role of methionine containing antioxidant combination in the management of pain in chronic pancreatitis: a systematic review and meta-analysis. Pancreatology. 2015 Mar-Apr;15(2):136-44. doi: 10.1016/j.pan.2015.01.003. Epub 2015 Jan 21.
• Hallstrom H, Norrbrink C. Screening tools for neuropathic pain: can they be of use in individuals with spinal cord injury? Pain. 2011 Apr;152(4):772-779. doi: 10.1016/j.pain.2010.11.019. Epub 2011 Jan 26.
• Fitzsimmons D, Kahl S, Butturini G, van Wyk M, Bornman P, Bassi C, Malfertheiner P, George SL, Johnson CD. Symptoms and quality of life in chronic pancreatitis assessed by structured interview and the EORTC QLQ-C30 and QLQ-PAN26. Am J Gastroenterol. 2005 Apr;100(4):918-26. doi: 10.1111/j.1572-0241.2005.40859.x.
• • S Sarkar, D Hazarika, A Adak, P Sarkar, M Khan, NR Duvvur, R Talukdar. Impact of Personalized Counseling on Depression and Quality of Life in Patients with Chronic Pancreatitis: Results from a Randomized Controlled Trial Gastroenterology 156 (6), S-166.
• • S Sarkar, N Reddy, R Talukdar. Determinants of depression and its impact on quality of life in patients with chronic pancreatitis. Gut 67 (Suppl 2), A79-A80.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 27, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 4, 2020

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 27, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: pain; quality of life; depression; anxiety; magnetic resonance spectroscopy; metabolome; chronic pancreatitis; quantitative sensory testing
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Behavioral Symptoms; Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Depression; Pancreatitis, Chronic
• Other Study ID Numbers: PEPCP2023 ver 04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: If other researchers collaborate with us in the future for similar research project, we will share de-identified data pertaining to patients clinical characteristics as per requirement of the study design.
• IPD Sharing Time Frame: After completion of study to one year thereafter.
• IPD Sharing Access Criteria: Collaborative study with similar study design/outcomes
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No