Personalized Education and Pain Response in Chronic Pancreatitis

Not Applicable

Not yet recruiting

• Conditions: Pain Syndrome; Depression, Anxiety; Chronic Pancreatitis

• Registration Number: NCT04654377
• Lead Sponsor: Asian Institute of Gastroenterology, India

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-11-27
• Study First Submitted QC: 2020-12-03
• Study First Posted: 2020-12-04
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-27
• Last Update Posted: 2025-07-30
• Study Start: 2025-08-01
• Primary Completion: 2026-07-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 114

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in pain score	3 and 6 months	Pain will be measured using the Visual analog scale (0-10)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Asian Institute of Gastroenterology; 🇮🇳 Hyderabad, Telangana, India