A Single-center, Prospective Cohort Study on the Differentiation of Benign and Malignant Bile Duct Stenosis Based on Bile and Peripheral Blood cfDNA Methylation Profiles

NCT06115655 | Unknown DMC

• 1 other identifier: KY20232312
• Study Type: observational
• Target: 161
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to detect the methylation characteristics of cfDNA in the bile and plasma of patients with bile duct stricture. The main question it aims to answer is: Can the developed model, using peripheral blood and bile cell-free DNA sequencing, work well in screening and classifying unknown biliary stricture? Participants will collect approximately 10ml of peripheral blood and 5ml of bile from the patient.

Conditions

Bile Duct Neoplasms; Jaundice, Obstructive; Bile Duct Diseases

Keywords

Methylation; Liquid Biopsy; Cell-Free Nucleic Acids; Cancer Diagnosis

Outcome Measures

Primary Outcomes (3)

• Diagnostic accuracy

  This refers to the ability of the test (cell-free DNA sequencing) to correctly classify individuals into the categories of having or not having the disease. It is a measure of the test's overall effectiveness. The reference test is histological test for cancers or one-year follow-up for non-cancers.

  Immediately after test completion

• Sensitivity

  This is the ability of the test (cell-free DNA sequencing) to correctly identify those with the disease. It is the proportion of true positive results (those with the disease who test positive) to the total number of individuals who actually have the disease. The reference test is histological test for cancers or one-year follow-up for non-cancers.

  Immediately after test completion

• Specificity

  This is the ability of the test (cell-free DNA sequencing) to correctly identify those without disease. It is the proportion of true negative results (those without the disease who test negative) to the total number of individuals who actually do not have the disease. The reference test is histological test for cancers or one-year follow-up for non-cancers.

  Immediately after test completion

Study Arms (2)

malignant patients

The presence of biliary stricture due to malignant diseases, such as cholangiocarcinoma.

Diagnostic Test: cfDNA methylation detection

benign patients

The presence of biliary stricture due to benign diseases, such as inflammation.

Diagnostic Test: cfDNA methylation detection

Interventions

cfDNA methylation detection DIAGNOSTIC_TEST

Extract cfDNA from bile and plasma, and perform methylation detection.

benign patients; malignant patients

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

According to the "Sample Size Calculation for Comparative Diagnostic Studies with Categorical Variables (Rates)" method, it is calculated. Based on the previous research results, it is estimated that the diagnostic sensitivity of sequencing methylation profiles in bile cfDNA is 82%, the specificity is 95%, the allowable error in sensitivity is 0.1, the allowable error in specificity is 0.1, α is set to 0.05, the loss to follow-up rate is 10%, and the calculated sample size is approximately 161 cases.

You may qualify if:

• \. Patients with biliary stricture aged between 18 and 90 years old.
• \. Patients scheduled to undergo ERCP surgery due to obstructive jaundice or cholangitis.
• \. Definite benign or malignant diagnosis: with a pathological diagnosis of benign or malignant disease, or with follow-up data indicating a benign or malignant diagnosis.

You may not qualify if:

• \. Receive radiotherapy, chemotherapy, or targeted therapy before sampling.
• \. Malignant tumors in other parts of the body (not related to biliary stricture).
• \. Unable to determine the nature of the biliary stricture.
• \. Ineligible for ERCP due to systemic conditions or gastrointestinal obstruction.
• \. Pregnant or breastfeeding women.
• \. Unable to sign the informed consent form.

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (1)

The First Affiliated Hospital of the Air Force Medical University

Xi'an, Shaanxi, 710032, China

RECRUITING

Related Publications (7)

• Dorrell R, Pawa S, Zhou Y, Lalwani N, Pawa R. The Diagnostic Dilemma of Malignant Biliary Strictures. Diagnostics (Basel). 2020 May 25;10(5):337. doi: 10.3390/diagnostics10050337.

  PMID: 32466095 BACKGROUND

• Dumonceau JM, Delhaye M, Charette N, Farina A. Challenging biliary strictures: pathophysiological features, differential diagnosis, diagnostic algorithms, and new clinically relevant biomarkers - part 1. Therap Adv Gastroenterol. 2020 Jun 16;13:1756284820927292. doi: 10.1177/1756284820927292. eCollection 2020.

  PMID: 32595761 BACKGROUND

• Sun B, Moon JH, Cai Q, Rerknimitr R, Ma S, Lakhtakia S, Ryozawa S, Kutsumi H, Yasuda I, Shiomi H, Li X, Li W, Zhang X, Itoi T, Wang HP, Qian D, Wong Lau JY, Yang Z, Ji M, Hu B; Asia-Pacific ERCP Club. Review article: Asia-Pacific consensus recommendations on endoscopic tissue acquisition for biliary strictures. Aliment Pharmacol Ther. 2018 Jul;48(2):138-151. doi: 10.1111/apt.14811. Epub 2018 Jun 7.

  PMID: 29876948 BACKGROUND

• Davalos V, Esteller M. Cancer epigenetics in clinical practice. CA Cancer J Clin. 2023 Jul-Aug;73(4):376-424. doi: 10.3322/caac.21765. Epub 2022 Dec 13.

  PMID: 36512337 BACKGROUND

• Vedeld HM, Grimsrud MM, Andresen K, Pharo HD, von Seth E, Karlsen TH, Honne H, Paulsen V, Farkkila MA, Bergquist A, Jeanmougin M, Aabakken L, Boberg KM, Folseraas T, Lind GE. Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile. Hepatology. 2022 Jan;75(1):59-73. doi: 10.1002/hep.32125. Epub 2021 Dec 5.

  PMID: 34435693 BACKGROUND

• Goeppert B, Stichel D, Toth R, Fritzsche S, Loeffler MA, Schlitter AM, Neumann O, Assenov Y, Vogel MN, Mehrabi A, Hoffmann K, Kohler B, Springfeld C, Weichenhan D, Plass C, Esposito I, Schirmacher P, von Deimling A, Roessler S. Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis. Gut. 2022 Feb;71(2):391-401. doi: 10.1136/gutjnl-2020-322983. Epub 2021 Jan 19.

  PMID: 33468537 BACKGROUND

• Colyn L, Barcena-Varela M, Alvarez-Sola G, Latasa MU, Uriarte I, Santamaria E, Herranz JM, Santos-Laso A, Arechederra M, Ruiz de Gauna M, Aspichueta P, Canale M, Casadei-Gardini A, Francesconi M, Carotti S, Morini S, Nelson LJ, Iraburu MJ, Chen C, Sangro B, Marin JJG, Martinez-Chantar ML, Banales JM, Arnes-Benito R, Huch M, Patino JM, Dar AA, Nosrati M, Oyarzabal J, Prosper F, Urman J, Cubero FJ, Trautwein C, Berasain C, Fernandez-Barrena MG, Avila MA. Dual Targeting of G9a and DNA Methyltransferase-1 for the Treatment of Experimental Cholangiocarcinoma. Hepatology. 2021 Jun;73(6):2380-2396. doi: 10.1002/hep.31642.

  PMID: 33222246 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

10ml peripheral venous blood sample and 5ml bile from each participant.

MeSH Terms

Conditions

Bile Duct Neoplasms; Jaundice, Obstructive; Bile Duct Diseases

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Jaundice; Hyperbilirubinemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Study Officials

• Yanglin Pan, MD

  The First Affiliated Hospital of the Air Force Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanglin Pan, MD

CONTACT

+86-13991811225; panyl@fmmu.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 30, 2023
• First Posted: November 3, 2023
• Study Start: October 1, 2023
• Primary Completion: October 1, 2024
• Study Completion: October 30, 2024
• Last Updated: November 3, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)