search
Back to results

Novel Urine-Based DNA Methylation Biomarkers for Urothelial Bladder Carcinoma Detection in Patients With Hematuria

Primary Purpose

Bladder Cancer

Status
Completed
Phase
Not Applicable
Locations
Egypt
Study Type
Interventional
Intervention
Cystoscopy
Computed tomography
DNA hypermethylation assay
Urine cytology
Sponsored by
Mansoura University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Bladder Cancer focused on measuring Urothelial bladder carcinoma, Bladder cancer, Hematuria, Biomarkers, DNA methylation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)Does not accept healthy volunteers

Inclusion Criteria:

  • patients with hematuria (macroscopic or microscopic)

Exclusion Criteria:

  • history of Bladder Cancer
  • history of pelvic irradiation,
  • bleeding diathesis or receiving anticoagulants
  • patients with upper urinary tract neoplasm or urolithiasis

Sites / Locations

  • Mansoura Urology and Nephrology Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hematuria patients

Arm Description

Voided urine was collected from consecutive patients presented with hematuria at our institute for urine cytology and DNA hypermethylation assay of the assigned genes using methylation-specific Polymerase Chain Reaction (PCR). Further assessment by office cystoscopy and imaging with subsequent inpatient cystoscopic biopsy for positive findings, was done. The diagnostic characteristics of DNA hypermethylation and urine cytology were assessed based on its capability to predict UBC noninvasively

Outcomes

Primary Outcome Measures

Rate of hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) in patients with urothelial bladder carcinoma
Rate of hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) in patients with urothelial bladder carcinoma

Secondary Outcome Measures

Full Information

First Posted
April 27, 2022
Last Updated
April 30, 2022
Sponsor
Mansoura University
search

1. Study Identification

Unique Protocol Identification Number
NCT05362539
Brief Title
Novel Urine-Based DNA Methylation Biomarkers for Urothelial Bladder Carcinoma Detection in Patients With Hematuria
Official Title
Novel Urine-Based DNA Methylation Biomarkers for Urothelial Bladder Carcinoma Detection in Patients With Hematuria
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
February 1, 2019 (Actual)
Primary Completion Date
June 1, 2021 (Actual)
Study Completion Date
April 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mansoura University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The current study aimed to assess the diagnostic performance of novel urine-based DNA hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) for UBC detection in patients with hematuria.
Detailed Description
According to GLOBOCAN data, bladder cancer (BC) is considered a major health problem that represents 3% of all cancer diagnoses. Urothelial bladder carcinoma (UBC) accounts for the vast majority (>90%) of BC cases with predominance of non-muscle invasive disease (Ta, Tis or T1) in 75% of patients while others show muscle invasion (T2-4). In refereed population, UBC is usually diagnosed as a result of work-up for hematuria at a rate of 2-5% following an evaluation of asymptomatic microscopic hematuria, and, up to 5-15% of patients with macroscopic hematuria. Therefore, a timely prompt evaluation of hematuria can give to earlier diagnosis and better survival of UBC. Currently, cystoscopy /cross sectional imaging are the gold standard tools for UBC diagnosis in patients with hematuria. Unfortunately, these costly, invasive and painful diagnostics could miss early, small/flat bladder lesions. Urine cytology has been proposed as a non-invasive alternative test with high specificity, however, it lacks sensitivity for diagnosis of low grade (LG) tumors. Over the last decades, multiple researches have output different markers for UBC diagnosis. Based on their target of assessment, these markers include screening for soluble antigens (BTA-Stat, NMP-22, surviving, etc.), cell surface antigens (Cytokeratins and UroVysion), genomic markers (Cxbladder and Xpert) and urinary metabolomics (CRAT and SLC25A20). However, most of these markers are limited by unsatisfying diagnostic performance, high cost or lack of validation. Several preliminary studies have shown that DNA methylation, a critical step in transcription regulation, is chemically stable and can be precisely quantified, making it an attractive marker for UBC detection. Both local and global DNA hypermethylation in BC specimens are usually associated with inactivation of tumor suppressor genes. These methylations changes could be effectively identified in urine sediments as well as tumor tissues. In the current literature, multiple studies investigated the performance of DNA hypermethylation of either individual or panel genes with reported sensitivity (SN) and specificity (SP) values that range from 40-95 % and 10-100 %, respectively. Most of these studies were limited by tumor characteristics heterogeneity (majority were ≥T2 and high grade (HG) disease; which did not reflect the daily practice, inclusion of different BC histological variants), lack of external validation and small sample size. The aim of our study is to assess the diagnostic performance of novel urine-based DNA methylation six genes (GATA4, P16, P14, APC, CDH1 and CD99) for UBC detection in patients with hematuria. Moreover, we investigated the methylation pattern of these genes in different stages and grades of UBC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
Urothelial bladder carcinoma, Bladder cancer, Hematuria, Biomarkers, DNA methylation

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
246 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hematuria patients
Arm Type
Experimental
Arm Description
Voided urine was collected from consecutive patients presented with hematuria at our institute for urine cytology and DNA hypermethylation assay of the assigned genes using methylation-specific Polymerase Chain Reaction (PCR). Further assessment by office cystoscopy and imaging with subsequent inpatient cystoscopic biopsy for positive findings, was done. The diagnostic characteristics of DNA hypermethylation and urine cytology were assessed based on its capability to predict UBC noninvasively
Intervention Type
Procedure
Intervention Name(s)
Cystoscopy
Intervention Description
diagnostic cystoscopy for detection of any bladder lesions
Intervention Type
Diagnostic Test
Intervention Name(s)
Computed tomography
Intervention Description
Computed tomography for patients to exclude bladder lesions
Intervention Type
Genetic
Intervention Name(s)
DNA hypermethylation assay
Intervention Description
DNA hypermethylation assay of six genes (GATA4, P16, P14, APC, CDH1 and CD99)
Intervention Type
Diagnostic Test
Intervention Name(s)
Urine cytology
Intervention Description
voided urine cytology for all patients
Primary Outcome Measure Information:
Title
Rate of hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) in patients with urothelial bladder carcinoma
Description
Rate of hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) in patients with urothelial bladder carcinoma
Time Frame
4 weeks

10. Eligibility

Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: patients with hematuria (macroscopic or microscopic) Exclusion Criteria: history of Bladder Cancer history of pelvic irradiation, bleeding diathesis or receiving anticoagulants patients with upper urinary tract neoplasm or urolithiasis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amr A Elsawy
Organizational Affiliation
Mansoura University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mansoura Urology and Nephrology Center
City
Mansoura
State/Province
DK
ZIP/Postal Code
35516
Country
Egypt

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Novel Urine-Based DNA Methylation Biomarkers for Urothelial Bladder Carcinoma Detection in Patients With Hematuria

We'll reach out to this number within 24 hrs