ERCP-induced and Non-ERCP Induced Acute Pancreatitis: Two Distinct Clinical and Immunological Entities?

Post-ERCP Acute Pancreatitis Clinical Trial

Official title:

Endoscopic Retrograde Cholangiopancreatography (ERCP)-Induced and Non-ERCP Induced Acute Pancreatitis: Two Distinct Clinical and Immunological Entities?

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02602574
• Other study ID #: PEP 2015
• Status: Enrolling by invitation
• Start date: January 31, 2018
• Est. completion date: January 2024

Study information

• Verified date: May 2022
• Source: University Hospital Rijeka
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Post endoscopic pancreatitis (PEP) has different initial immunologic response to primary injury compared to acute pancreatitis of other etiology (non-PEP AP).

The purpose of this study is to compare initial immunologic response, 24 h after primary injury, in patients with PEP and patients with acute pancreatitis of other etiology.

Description:

PROTOCOL:

All patients with indication for endoscopic retrograde cholangiopancreatography (ERCP) will be prepared for ERCP on the following protocol: they will be instructed not to eat 4 to 6 hours before the procedure. Immediately before the procedure they will be administrated with Diclophenac Sodium 100 mg suppositories. One hour before the procedure 10 mL of blood sample and urine sample will be taken and analyzed in laboratory premises incorporated in University Hospital Centre Rijeka for following parameters: values of amylase in serum and urine and lipase in serum, liver enzyme tests and kidney function. 4-6 hours after ERCP is performed, 10 mL of blood sample will be taken and analyzed in laboratory premises incorporated in University Hospital Centre Rijeka for following parameters: values of amylase in serum and urine and lipase in serum, liver enzyme tests and kidney function.

24 hours after the procedure all patients will be taken 30 ml of heparinized peripheral venous blood and urine sample. 10 mL will be examined in the Department of Laboratory Medicine, Clinical Hospital Centre for following parameters: values of amylase in serum and urine and lipase in serum, liver enzyme tests and kidney function. Urine sample collected after the procedure will be used to evaluate amylase levels. Other 20 mL of blood samples will be sent to Department of Physiology and Immunology, School of Medicine where immunologic analysis will be performed. All patients who underwent ERCP will be divided into two groups. First group (PEP group) will be made of patients who developed acute pancreatitis following ERCP. Upon clinical and laboratory confirmation of acute pancreatitis according to European Society of Gastrointestinal Endoscopy (ESGE) guidelines for post-ERCP pancreatitis, will be further monitored during hospitalization for evaluation of the severity of the disease. Severity of the disease will be assessed according to the Cotton criteria for the severity of post-ERCP pancreatitis. Group of patients who underwent ERCP but didn't develop acute pancreatitis within 24 hours after the procedure, according to ESGE guidelines will be used as a control group (non-PEP group).

All patients with acute pancreatitis according to Atlanta criteria admitted through Emergency Department will be taken 30 ml of heparinized peripheral venous blood and urine sample upon 24 hours after the clinical symptoms have started (upper abdominal pain often radiating through to the back). 10 mL of collected blood samples will be examined in the Department of Laboratory Medicine, Clinical Hospital Centre for following parameters: values of amylase in serum and urine and lipase in serum, liver enzyme tests and kidney function. Other 20 mL of blood samples will be sent to Department of Physiology and Immunology, School of Medicine where immunologic analysis will be performed. This group of patients will be further monitored during hospitalization for evaluation of the severity of the disease. Severity of the disease will be assessed according to the Atlanta criteria.

METHODS AND MATERIALS

Laboratory parameters

For each patient included in the study blood and urine analysis will be performed in the Department of Laboratory Medicine, Clinical Hospital Centre Rijeka. Basic hematology tests will include: total blood count - a count of the total number of red blood cells, white blood cells and platelets present in blood, values of hemoglobin and hematocrit. Biochemical analysis of blood serum will include: values of amylase and lipase in serum, sodium, potassium, glucose, liver enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gama-glutamyl transferase (GGT), alkaline phosphatase (ALP)) direct and indirect bilirubin, kidney function (serum urea and creatinine, estimated glomerular filtration (eGFR)), C-reactive protein and acid-base status of arterial blood.

Immunological methods

For each patient included in the study immunologic analysis of blood samples (24 hours after the procedure or onset of the symptoms) will be performed in Department of Physiology and Immunology, School of Medicine in Rijeka, Croatia.

Isolation of peripheral blood mononuclear cells Twenty milliliters of peripheral blood will be acquired in Vacutainer (Becton Dickinson, Franklin Lakes, NY), overlaid onto Lymphoprep (Nycomed Pharma AS, Oslo, Norway) and centrifuged (20 min at 600 g). After the centrifugation, the cells from the interface will be collected and washed twice in Roswell Park Memorial Institute (RPMI) 1640 medium (Auckland, NZ) and used immediately for further experimental procedure. The viability of the cells was >95% will be assessed with propidium iodide 0.5 mg/ml/106 cells (Sigma-Aldrich Chemie) and a flow cytometer (FACSCalibur, Becton Dickinson, San Jose, USA)

Detection of cell surface Peripheral blood mononuclear cells (PBMC) will be stained for 30 min at 40 degrees Celsius with different combinations of Phycoerythrin (PE) - Cyanine (Cy) anti-cluster of differentiation (CD) 3 monoclonal antibody (mouse Antibody (mAb), Immunoglobulin G 1 (IgG1)), PE-conjugated anti-cluster of differentiation (CD)56 mAb (mouse B159, IgG1) and fluorescein isothiocyanate (FITC)-conjugated anti-natural-killer group 2, member D (NKG2D) mAb (5C6). FITC-, PE- and PE-Cy conjugated mouse isotype match antibodies will be used to set negative controls for each class of antibody used.

Stained cell samples will be analyzed by flow cytometry using FACSCalibur flow cytometer (Becton Dickinson & Co, San Jose, USA).

Detection of cytokine Interleukin (IL)-1 beta (β) and heat shock protein (HSP) 70, 27.

For the quantitative determination of human IL-1 β concentrations in plasma,Human IL-1 ELISA (Enzyme-Linked Immunosorbent Assay) Kit will be used.

For the quantitative determination of heat shock protein (HSP) 70 and 27 in plasma, HSP 70 High sensitivity ELISA Kit and HSP 27 ELISA kit will be used.

Detection of pentraxin 3 (PTX 3) and procalcitonin For the quantitative determination of human pentraxin 3 (PTX) and procalcitonin concentrations in plasma specific ELISA Kit will be used.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 66
• Est. completion date: January 2024
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• all patients underwent to ERCP irrespectively about the diagnosis

• all patients with diagnosed acute pancreatitis according to Atlanta criteria admitted through Emergency Department within 24 hours of onset of symptoms.

Exclusion Criteria:

• unwillingness or inability to consent for the study

• anticipated inability to follow protocol, previous ERCP, acute cholecystitis and/or cholangitis

• active or recent (within 4 weeks) gastrointestinal hemorrhage

• existing acute pancreatitis (lipase peak) within 72 hours prior to ERCP

• intrauterine pregnancy, breast feeding mother

• patients with chronic inflammatory diseases (e.g. IBD) systemic inflammatory and autoimmune disorders (e.g. systemic lupus erythematosus, ) or acute inflammatory diseases (e.g. pneumonia, pyelonephritis or sepsis of any cause)

• patients on immunomodulatory or immunosuppressive therapy.

Related Conditions & MeSH terms

• Pancreatitis
• Post-ERCP Acute Pancreatitis

Intervention

Other:
• heparinized peripheral venous blood and urine sample.
All patients will be taken heparinized peripheral venous blood and urine sample

Locations

Country	Name	City	State
Croatia	Clinical Hospital Centre	Rijeka	Kresimirova 42

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Rijeka

Country where clinical trial is conducted

Croatia, 

References & Publications (8)

Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25. — View Citation

Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, Liguory C, Nickl N. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991 May-Jun;37(3):383-93. Review. — View Citation

Demols A, Deviere J. New frontiers in the pharmacological prevention of post-ERCP pancreatitis: the cytokines. JOP. 2003 Jan;4(1):49-57. Review. — View Citation

Dumonceau JM, Andriulli A, Elmunzer BJ, Mariani A, Meister T, Deviere J, Marek T, Baron TH, Hassan C, Testoni PA, Kapral C; European Society of Gastrointestinal Endoscopy. Prophylaxis of post-ERCP pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - updated June 2014. Endoscopy. 2014 Sep;46(9):799-815. doi: 10.1055/s-0034-1377875. Epub 2014 Aug 22. — View Citation

Fung AS, Tsiotos GG, Sarr MG. ERCP-induced acute necrotizing pancreatitis: is it a more severe disease? Pancreas. 1997 Oct;15(3):217-21. — View Citation

Kylänpää L, Rakonczay Z Jr, O'Reilly DA. The clinical course of acute pancreatitis and the inflammatory mediators that drive it. Int J Inflam. 2012;2012:360685. doi: 10.1155/2012/360685. Epub 2012 Dec 12. — View Citation

Testoni PA, Vailati C, Giussani A, Notaristefano C, Mariani A. ERCP-induced and non-ERCP-induced acute pancreatitis: Two distinct clinical entities with different outcomes in mild and severe form? Dig Liver Dis. 2010 Aug;42(8):567-70. doi: 10.1016/j.dld.2009.10.008. Epub 2009 Dec 16. — View Citation

Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013 Jun;144(6):1252-61. doi: 10.1053/j.gastro.2013.01.068. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of initial immunologic response in patients with PEP and patients with AP of other etiology (Number of Participants With Abnormal Laboratory Values)	Number of Participants With Abnormal Laboratory Values	24 hours after the primary injury
Secondary	Correlation between differences in initial inflammatory response and clinical outcomes of AP (biliary and alcoholic) and PEP (Number of Participants With Abnormal Laboratory Values)	Number of Participants With Abnormal Laboratory Values	1 month