Personalized Education and Pain Response in Chronic Pancreatitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Chronic Pancreatitis, Pain Syndrome, Depression, Anxiety

Intervention / Treatment
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* Other: Personalised education


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Personalised education<br>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<br>* Patients will be explained about their disease and possible outcomes based on clinical, biochemical and imaging data.<br>|
| No Intervention: Standard communication<br>Greetings Recording clinical/imaging data. Administration of questionnaire. Addressing general queries from patients and care givers. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain score | Pain will be measured using the Izbicki pain score | 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 number of hospitalisations | The patient will record the number of painful days in a self reported hospitalisation questionnaire. | 3 and 6 months | 
| Change in neuropathic pain | Neuropathic pain will be evaluated using quantitative sensory testing (QST) | 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 Patient's Health Questionnaire (PHQ) tools. | 3 and 6 months | 
| Change in depression score | Depression will be measured using Hamilton Depression (HAM-D) tools. | 3 and 6 months | 
| Change in anxiety score | Anxiety will be measured using the Hospital anxiety and depression (HAD) tools. | 3 and 6 months | 
| 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 | 
| Change in urinary metabolites | Urinary neurotransmitters and amino acids will be measured using Liquid chromatography with mass spectrometry (LC-MS). | 3 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, chronic pancreatitis, depression, anxiety, quality of life, metabolome, magnetic resonance spectroscopy, quantitative sensory testing