Personalized Education and Pain Response in Chronic Pancreatitis (PEPCP)

• ClinicalTrials.gov Identifier: NCT04654377
• Recruitment Status: Recruiting
• First Posted: December 4, 2020
• Last Update Posted: July 7, 2021
• Sponsor: Asian Institute of Gastroenterology, India
• Information provided by (Responsible Party): Rupjyoti Talukdar, Asian Institute of Gastroenterology, India

Study Description

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 5 episodes of abdominal pain of over the past 6 months.

Condition or disease	Intervention/treatment	Phase
Chronic Pancreatitis; Pain Syndrome; Depression, Anxiety	Other: Personalised education	Not Applicable

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 approaches. 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.

One aspect that is often overlooked in studies involving pain mechanisms and management. 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 5 episodes of abdominal pain of over the past 6 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Impact of Personalized Education on Pain Response in Patients With Chronic Pancreatitis (PEPCP)
• Actual Study Start Date: June 29, 2021
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Personalised education; Greetings; Recording clinical/imaging data.; Questionnaires administration.; Explaining the disease and possible outcome in the context of clinical/lab/imaging data.; Answering specific queries from patients 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 clinical/imaging data.; Administration of questionnaire.; Addressing general queries from patients and care givers.

Outcome Measures

Primary Outcome Measures :

1. Change in pain score [ Time Frame: 3 and 6 months ]
   Pain will be measured using the Izbicki pain score

Secondary Outcome Measures :

1. Change in number of painful days [ Time Frame: 3 and 6 months ]
   The patient will record the number of painful days in a self reported pain questionnaire.
2. Change in number of hospitalisations [ Time Frame: 3 and 6 months ]
   The patient will record the number of painful days in a self reported hospitalisation questionnaire.
3. Change in neuropathic pain [ Time Frame: 3 and 6 months ]
   Neuropathic pain will be evaluated using quantitative sensory testing (QST)
4. Change in neuropathic pain [ Time Frame: 3 and 6 months ]
   Neuropathic pain will be evaluated using the PainDetect tool
5. Change in quality of life (QOL) [ Time Frame: 3 and 6 months ]
   Quality of life (QOL) will be measured using the EORTC QLQ 30
6. Change in depression score [ Time Frame: 3 and 6 months ]
   Depression will be measured using Beck depression Inventory (BDI) II
7. Change in depression score [ Time Frame: 3 and 6 months ]
   Depression will be measured using Patient's Health Questionnaire (PHQ) tools.
8. Change in depression score [ Time Frame: 3 and 6 months ]
   Depression will be measured using Hamilton Depression (HAM-D) tools.
9. Change in anxiety score [ Time Frame: 3 and 6 months ]
   Anxiety will be measured using the Hospital anxiety and depression (HAD) tools.
10. Change in brain metabolites [ Time Frame: 3 months ]
    Metabolites (creatine, Glutamate/Glutamate, myoinositol, N-acetyl aspartate, choline) with be evaluated in the hippocampus, basal ganglia, prefrontal cortex, anterior cingulate cortex using magnetic resonance spectroscopy (MRS).
11. Change in urinary metabolites [ Time Frame: 3 months. ]
    Urinary neurotransmitters and amino acids will be measured using Liquid chromatography with mass spectrometry (LC-MS).

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Chronic pancreatitis of at least 3 years
• At least 5 episodes of pain in the past 6 months
• Pain score of at least 3 on a visual analog scale (VAS) of 0-10
• Age 18-60yrs
• Both genders

Exclusion Criteria:

• Acute pancreatitis episode at the time of enrolment and/or during follow-up.
• Ongoing pain 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.

Contacts and Locations

Contacts

Contact: Rupjyoti Talukdar, MD, FICP, AGAF; 7032804231; rup_talukdar@yahoo.com

Locations

India

Asian Institute of Gastroenterology; Recruiting

Hyderabad, Telangana, India, 500032

Contact: Rupjyoti Talukdar, MD, FICP, AGAF +917032804231 rup_talukdar@yahoo.com

Sponsors and Collaborators

Asian Institute of Gastroenterology, India

Investigators

• Principal Investigator: Rupjyoti Talukdar, MD, FICP, AGAF; Asian Institute of Gastroenterology

More Information

Publications:

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. Review.

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.

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. Epub 2007 Jan 25.

Ceyhan GO, Demir IE, Rauch U, Bergmann F, Müller MW, Büchler MW, Friess H, Schäfer 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. Review.

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. Review.

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.

Hallström 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.

• 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.

• Responsible Party: Rupjyoti Talukdar, Director, Pancreatology; Head, Pancreas Research Group and Division of Gut Microbiome Research, Asian Institute of Gastroenterology, India
• ClinicalTrials.gov Identifier: NCT04654377
• Other Study ID Numbers: PEPCP2020 ver 01
• First Posted: December 4, 2020
• Last Update Posted: July 7, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: After completion of study to one year thereafter.
• Access Criteria: Collaborative study with similar study design/outcomes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rupjyoti Talukdar, Asian Institute of Gastroenterology, India:

chronic pancreatitis; pain; depression; anxiety; quality of life; metabolome; magnetic resonance spectroscopy; quantitative sensory testing

Additional relevant MeSH terms:

Pancreatitis; Pancreatitis, Chronic; Depression; Behavioral Symptoms; Pancreatic Diseases; Digestive System Diseases