Personalized Education and Pain Response in Chronic Pancreatitis

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

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

Первичные конечные точки

• Change in pain score [Срок оценки: 3 and 6 months]

Вторичные конечные точки (12)

• Change in number of painful days [Срок оценки: 3 and 6 months]
• Change in the number of hospital visits [Срок оценки: 3 and 6 months]
• Change in neuropathic pain [Срок оценки: 3 and 6 months]
• Change in quality of life (QOL) [Срок оценки: 3 and 6 months]
• Change in depression score [Срок оценки: 3 and 6 months]
• Change in depression score [Срок оценки: 3 and 6 months]
• Change in anxiety score [Срок оценки: 3 and 6 months]
• Change in multidimensional aspects of pain [Срок оценки: 3 and 6 months]
• Change in the psychological aspects of pain [Срок оценки: 3 and 6 months]
• Change in sleep behaviour [Срок оценки: 3 and 6 months]
• Change in the patient's perception of alteration in pain [Срок оценки: 3 and 6 months]
• Difference in analgesic requirement [Срок оценки: 3 and 6 months]

Критерии участия

Критерии включения

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

Критерии исключения

• 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..

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Индия · 1 центр

• Asian Institute of Gastroenterology — Hyderabad

Публикации

• 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. PMID 24151350
• 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. PMID 23357056
• 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. PMID 17408654
• 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. PMID 19568227
• 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. PMID 20510829
• 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. PMID 25648074
• 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. PMID 21683078
• 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. PMID 7667246

Идентификаторы

NCT: NCT04654377 · PEPCP2023 ver 04

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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