A Prospective Study of UCAD for Diagnosing Benign or Malignant Biliary Obstruction and Follow-up

January 12, 2023 updated by: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

A Prospective, Multi-centre, Single-blinded Study of UCAD for Diagnosing Benign or Malignant Biliary Obstruction and Follow-up

Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Analyzing CIN of the DNA extracted from bile tract exfoliated cells in bile samples seems a promising method for diagnosing, monitoring, and predicting the prognosis of patients with malignant biliary obstruction, including biliary tract cancer (BTC), pancreatic head carcinoma. CIN can be assessed using experimental techniques such as bulk DNA sequencing, fluorescence in situ hybridization (FISH), or conventional karyotyping. However, these techniques are either time-consuming or non-specific. The investigators here intend to study whether a new method named Ultrasensitive Chromosomal Aneuploidy Detection (UCAD), which is based on low-coverage whole-genome sequencing, can be used to analyze CIN thus helping diagnose malignant biliary obstruction and assessing follow-up.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related to metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells, it is a potentially non-invasive way to detect CIN in the bile tract exfoliated cells in bile samples for diagnosing and monitoring malignant biliary obstruction patients. UCAD is a new method to detect CIN in the DNA sample from patients, including extracting DNA from bile, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of malignant biliary obstruction patients. The investigators intended to conduct a prospective, single-blinded study by analyzing bile samples from malignant biliary obstruction patients and control groups without any tumor in the biliary system or other organs to compare the specificity and sensitivity of the UCAD test for diagnosing malignant biliary obstruction to other modalities, such as bile cytology. The investigators also intend to investigate the potential of UCAD in malignant biliary obstruction patient follow-up by analyzing the CIN level and following malignant biliary obstruction patients for up to 2 years to determine if there is a correlation between CIN level and patient prognosis

Study Type

Observational

Enrollment (Anticipated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Tianyu Zhai, M.D., Ph.D.
  • Phone Number: +8619916934772
  • Email: 937554343@qq.com

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200092
        • Recruiting
        • Xinhua Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with malignant biliary obstruction or participants in control group from February 2022 till the end of this study in 11 hospitals including Xinhua Hospital, Shanghai Zhongshan Hospital, Ruijin Hospital, Changhai Hospital, Shanghai Changzheng Hospital, Eastern Hepatobiliary Surgery Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Jiangsu Provincial Hospital, The Third Affiliated Hospital of Sun Yat-Sen University, Tianjin Medical University Second Hospital, First Affiliated Hospital of Zhejiang University.

Description

Inclusion Criteria:

  • Patients diagnosed with malignant biliary obstruction and planned to undergo ERCP(endoscopic retrograde cholangiopancreatography), PTCS(percutaneous transhepatic cholangioscopy) or surgery.
  • Malignant biliary obstruction patients confirmed by operation or biopsy.
  • Participants without any tumor disease and willing to attend the study.
  • Male or female patients aged >= 18 years.
  • Participants signed informed consent form.

Exclusion Criteria:

  • Patients diagnosed with malignant biliary obstruction and planned to undergo ERCP, PTCS or surgery.
  • Malignant biliary obstruction patients confirmed by operation or biopsy.
  • Participants without any tumor disease and willing to attend the study.
  • Male or female patients aged >= 18 years.
  • Participants signed informed consent form.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
malignant biliary obstruction
Pre-surgery patients with malignant biliary obstruction will be the experimental group to determine the sensitivity and specificity of UCAD analysis, the result will be compared with cytology.
Diagnostic test: The level of CIN
The extracted DNA from bile will be analyzed by UCAD to determine the level of CIN. And the patient will be followed for up to 2 years.
Benign biliary obstruction
Patients being treated for other biliary diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UCAD analysis.
Diagnostic test: The level of CIN
The extracted DNA from bile will be analyzed by UCAD to determine the level of CIN. And the patient will be followed for up to 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity and Specificity of UCAD analysis
Time Frame: through study completion, an average of 30 months
number of patients "declared positive" with the UCAD test among the patients who suffered from malignant biliary obstruction and number of patients "declared negative" with the UCAD test among the patients without cancer
through study completion, an average of 30 months
Assess the value of UCAD for malignant biliary obstruction patient follow-up
Time Frame: through study completion, an average of 30 months
Compare the CIN level with the patient information gathered by follow-up to determine whether there is a correlation between CIN level and patient prognosis , like PFS(progression-free survival), five-year survival rate.
through study completion, an average of 30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of the correlation between the level of CIN and the grade of the tumor sample
Time Frame: through study completion, an average of 30 months
level of CIN in the bile sample compared with the grade of the tumor confirmed by histopathologic examination, like Grade 1-4.
through study completion, an average of 30 months
Identification of the correlation between the level of CIN and the stage of the tumor sample
Time Frame: through study completion, an average of 30 months
level of CIN in the bile sample compared with the TNM stage of the tumor confirmed by histopathologic examination, like Stage 0-IV.
through study completion, an average of 30 months
Comparison of the sensitivity and specificity of the UCAD analysis versus bile cytology
Time Frame: through study completion, an average of 30 months
number of patients "declared positive" with the UCAD analysis versus patients "declared positive" with the bile cytology and number of patients "declared negative" with the UCAD analysis versus patients " declared negative " with the bile cytology
through study completion, an average of 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Collaborators

Changhai Hospital
Shanghai Zhongshan Hospital
Southwest Hospital, China
West China Hospital
First Affiliated Hospital Xi'an Jiaotong University
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Ruijin Hospital
First Affiliated Hospital of Zhejiang University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Third Affiliated Hospital, Sun Yat-Sen University
Eastern Hepatobiliary Surgery Hospital
Shanghai Changzheng Hospital
Second Hospital of Jilin University
Jiangsu Provincial People's Hospital
Affiliated Hospital of North Sichuan Medical College

Investigators

  • Study Chair: Jiandong Jiandong, M.D., Ph.D., Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 3, 2021

Primary Completion (Anticipated)

September 1, 2023

Study Completion (Anticipated)

March 1, 2024

Study Registration Dates

First Submitted

January 24, 2022

First Submitted That Met QC Criteria

February 8, 2022

First Posted (Actual)

February 14, 2022

Study Record Updates

Last Update Posted (Estimate)

January 16, 2023

Last Update Submitted That Met QC Criteria

January 12, 2023

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XH-22-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

We will try to protect the information of the included participants

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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