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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
An European Multi-centre Cohort Study for Unravelling Pharmacokinetic and Genetic Factors Underlying Post-ERCP Pancreatitis

Conditions
-----------------
Post-ERCP Acute Pancreatitis

Intervention / Treatment
-----------------
* Diagnostic Test: Take blood samples


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PEP patients<br>Patients who develop PEP | Diagnostic Test: Take blood samples<br>* Blood samples are used to check for polymorphisms in NSAID metabolization genes and to determine the diclofenac levels.<br>|
| Control cohort<br>Patients who do not develop PEP | Diagnostic Test: Take blood samples<br>* Blood samples are used to check for polymorphisms in NSAID metabolization genes and to determine the diclofenac levels.<br>|

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 |