Extracellular vesicles and biliary stenoses

ISRCTN	ISRCTN66835592
DOI	https://doi.org/10.1186/ISRCTN66835592
Protocol serial number	N/A
Sponsor	Service of Gastroenterology and Hepatology
Funder	Geneva University Hospital

Submission date: 31/01/2017
Registration date: 02/02/2017
Last edited: 11/07/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Bile is a substance produced by the liver and stored in the gall bladder, which is secreted into the small intestine to help digest fats from the diet. Common bile duct stenosis is the narrowing of the bile duct which blocks bile from being released, leading to problems with digestion. This condition can be malignant (cancerous) or benign (non-cancerous), but this is very hard to determine and can only be done reliably through surgery. It is important to determine this as malignant bile duct stenosis could be a sign of pancreatic cancer. Studies have shown that cancer cells release more extracellular vesicles (EVs) (packages released by cells that surround the membrane) as compared to healthy cells. It is estimated that using EVs as a marker for malignancy through measuring specific markers found in the tissue can help differentiate between malignant and benign stenosis. This study aims to determine if the measurement of EV concentration in bile could improve determining between malignant and benign common bile duct stenosis.

Who can participate?
Adults over the age of 16 who require their bile duct to be unblocked (biliary catheterization)

What does the study involve?
Participants have their bile duct unblocked through an endoscopic procedure (a long thin tube that has a light and a camera inserted through a small incision) which uses a catheter (a long thin tube), that is inserted through a small incision in the abdomen, into the bile duct area to remove bile. Bile samples are taken and are sent to a laboratory for analysis. Participants are followed up for one year to make sure they do not have malignant bile duct stenosis.

What are the possible benefits and risks of participating?
There are no direct benefits or risks to participants.

Where is the study run from?
Geneva University Hospital (Switzerland)

When is the study starting and how long is it expected to run for?
August 2006 to December 2015

Who is funding the study?
Geneva University Hospital (Switzerland)

Who is the main contact?
Jean Louis Frossard
jean-louis.frossard@hcuge.ch

Contact information

Prof Jean Louis Frossard
Scientific

Service of Gastroenterology and Hepatology, Geneva University Hospitals
Genève
1211
Switzerland

Study information

Primary study design	Observational
Study design	Observational multi-center longitudinal case-control study
Secondary study design	Longitudinal study
Study type	Participant information sheet
Scientific title	Extracellular vesicles in human bile as a novel and accurate marker of malignant biliary stenoses
Study objectives	This study aims to determine if the measurement of EV concentration in bile could improve the clinical discrimination between malignant and nonmalignant CBD stenosis.
Ethics approval(s)	1. Ethical Committee Geneva,08/08/2006, ref: GE 04-091 2. Ethical Committee Université libre de Bruxelles, Erasmus Hosptial, 02/11/2009, ref: P2009/007, CCB B 40620095782
Health condition(s) or problem(s) studied	Common bile duct stenosis
Intervention	Participants undergo a biliary catheterization through endoscopic exploration of the biliary tract. This involves bile being removed from the common bile duct after it has been aspirated. Bile is aliquoted into eppendorf tubes (5ml) and frozen to -20 ºC and stored at a laboratory in Geneva. The bile samples examined through laboratory analysis for markers of malignant and nonmalignant common bile duct stenosis. The first ten consecutive patients are assigned to the discovery cohort together with ten bile duct stones patients (i.e., internal controls proven nonmalignant) before endoscopy. The remaining 30 patients are assigned to the verification cohort before endoscopy is performed. Final diagnosis is determined by pathological examination of tissue sample in all patients with common bile duct stenosis. Participants are are clinically followed up for 1 year to show no sign of malignancy with a common bile duct stenosis related to chronic pancreatitis. Follow up will include clinical history with patient interview, measurement of CA-19.9 and imaging modalities. For bile duct stone patients, the diagnosis is based on radiological and endoscopic features.
Intervention type	Other
Primary outcome measure(s)	1. Extracellular vesicles (EVs) are evaluated by transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) and through medical interviews at baseline and 12 months 2. Serum bilirubin and CA19.9 are measured in all patients at baseline
Key secondary outcome measure(s)	Performance of extracellular vesicles (EVs) is assessed through tumor markers (including CA19-9) at baseline
Completion date	31/12/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	50
Key inclusion criteria	1. Patients scheduled for biliary catheterism due to obstructive jaundice or cholestasis of biliary origin (suspicion of cancer, suspicion of stones, chronic pancreatitis) 2. Age > 16 years old
Key exclusion criteria	1. Less than 16 years old 2. Pregnant women
Date of first enrolment	02/11/2009
Date of final enrolment	31/12/2013

Locations

Countries of recruitment

Belgium
Switzerland

Study participating centres

Service of Gastroenterology and Hepatology

Geneva University Hospital
R G Perret Gentil 14
Genève
1211
Switzerland

Service of Gastroenterology

Erasme University Hospital
Route de Lennik 808
Brussels
10170
Belgium

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Jean Louis Frossard (jean-louis.frossard@hcuge.ch).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2017		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

11/07/2018: Publication reference added.