An European Multi-centre Cohort Study for Unravelling Pharmacokinetic and Genetic Factors Underlying Post-ERCP Pancreatitis (G-PEP)

Endoscopic retrograde cholangiopancreatography (ERCP) comes with a risk for post-ERCP pancreatitis (PEP), which accounts for considerable morbidity, high healthcare expenditure, and death. The pathophysiology of PEP and the underpinnings of the preventive effect of rectal NSAID (RN) is poorly understood. Guidelines advise to take preventive measures with a single dose of 100mg RN, peri-ERCP. While NSAID administration reduces the risk with 40%, PEP still occurs after ERCP. In addition, patients with a PEP history have a higher risk to develop recurrence after a subsequent ERCP. This might suggest that an underlying genetic risk may contribute to increasing the incidence of PEP in some patients.

Study Overview

• Status: Recruiting
• Conditions: Post-ERCP Acute Pancreatitis
• Intervention / Treatment: Diagnostic test: Take blood samples

Detailed Description

This study is a hypothesis driven and hypothesis free analyses of PEP risk variants. Integrative analysis of NSAID pharmacokinetics and-genetics in PEP patients.

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Mike de Jong, MD; Phone Number: 0031883207054; Email: mike.dejong@radboudumc.nl

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • Radboudumc
      • Contact: Mike de Jong, MD; Phone Number: 0031883207054; Email: mike.dejong@radboudumc.nl
      • Contact: Erwin van Geenen, MD, PhD; Phone Number: 0031243619190; Email: erwin.vangeenen@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 years or older with an indication to undergo an ERCP, without pancreatic cancer, chronic pancreatitis, altered anatomy of the upper digestive tract and an ongoing acute pancreatitis.

Description

Inclusion Criteria:

• Age ≥ 18 years
• written informed consent
• Indication to undergo an ERCP

Exclusion Criteria:

• Pancreatic cancer
• Chronic pancreatitis
• Ongoing acute pancreatitis
• Altered anatomy, defined as anatomical variations in which gall and/or pancreatic juices (in case of pancreatic duct interventions) do not enter the duodenum by way of the ampulla of Vater.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PEP patients; Patients who develop PEP	Diagnostic test: Take blood samples; Blood samples are used to check for polymorphisms in NSAID metabolization genes and to determine the diclofenac levels.
Control cohort; Patients who do not develop PEP	Diagnostic test: Take blood samples; Blood samples are used to check for polymorphisms in NSAID metabolization genes and to determine the diclofenac levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in SNP's in NSAID metabolization genes	Analyzing differences in polymorphisms in NSAID metabolization genes between PEP patients and control patients using Taqman assay. DNA will be isolated from blood samples and analyzed for SNP's of biotransformation enzymes such as UDP-Glucuronosyltransferase-2B7 (UGT2B7) and CYP2C9. This will be done using polymerase chain reaction (PCR) with fluorescent probes specific for a SNP (Taqman assay)	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diclofenac levels	Detection of diclofenac levels two hours after diclofenac administration. Levels will be measured in blood samples by high-performance liquid chromatography (HPLC).	2 hours
Correlation diclofenac levels and NSAID metabolization gene polymorphisms	To investigate whether there is a correlation between diclofenac levels and NSAID metabolism gene polymorphisms. Using an independent t-test, the investigators will try to find a significant correlation between the diclofenac levels and a difference in single nucleotide polymorphism (SNP).	1 month
Genes involved in development of PEP	To investigate whether the known genes involved in developing acute pancreatitis also are involved in developing PEP. DNA isolated from the blood samples will be analyzed by Miniseq-technique.	1 month

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Erwin van Geenen, MD, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis
• Other Study ID Numbers: 108224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The dataset used during this study is available from the corresponding author upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No