Personalized Education and Pain Response in Chronic Pancreatitis

Depression, Anxiety Clinical Trial

— PEPCP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04654377
• Other study ID #: PEPCP2020 ver 01
• Status: Recruiting
• Phase: N/A
• Start date: June 29, 2021
• Est. completion date: December 2021

Study information

• Verified date: July 2021
• Source: Asian Institute of Gastroenterology, India
• Contact: Rupjyoti Talukdar, MD, FICP, AGAF
• Phone: 7032804231
• Email: rup_talukdar[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• 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 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.

Related Conditions & MeSH terms

• Chronic Pancreatitis
• Depression
• Depression, Anxiety
• Pain Syndrome
• Pancreatitis
• Pancreatitis, Chronic

Intervention

Other:
• Personalised education
Patients will be explained about their disease and possible outcomes based on clinical, biochemical and imaging data.

Locations

Country	Name	City	State
India	Asian Institute of Gastroenterology	Hyderabad	Telangana

Sponsors (1)

Lead Sponsor	Collaborator
Asian Institute of Gastroenterology, India

Country where clinical trial is conducted

India, 

References & Publications (12)

• 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.

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pain score	Pain will be measured using the Izbicki pain score	3 and 6 months
Secondary	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
Secondary	Change in number of hospitalisations	The patient will record the number of painful days in a self reported hospitalisation questionnaire.	3 and 6 months
Secondary	Change in neuropathic pain	Neuropathic pain will be evaluated using quantitative sensory testing (QST)	3 and 6 months
Secondary	Change in neuropathic pain	Neuropathic pain will be evaluated using the PainDetect tool	3 and 6 months
Secondary	Change in quality of life (QOL)	Quality of life (QOL) will be measured using the EORTC QLQ 30	3 and 6 months
Secondary	Change in depression score	Depression will be measured using Beck depression Inventory (BDI) II	3 and 6 months
Secondary	Change in depression score	Depression will be measured using Patient's Health Questionnaire (PHQ) tools.	3 and 6 months
Secondary	Change in depression score	Depression will be measured using Hamilton Depression (HAM-D) tools.	3 and 6 months
Secondary	Change in anxiety score	Anxiety will be measured using the Hospital anxiety and depression (HAD) tools.	3 and 6 months
Secondary	Change in brain metabolites	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).	3 months
Secondary	Change in urinary metabolites	Urinary neurotransmitters and amino acids will be measured using Liquid chromatography with mass spectrometry (LC-MS).	3 months.