Bladder CancerNCT05362539
Novel Urine-Based DNA Methylation Biomarkers for Urothelial Bladder Carcinoma Detection in Patients With Hematuria
A study testing Cystoscopy, Computed tomography and DNA hypermethylation assay in people with Bladder Cancer, run by Mansoura University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Cystoscopy, Computed tomography and DNA hypermethylation assay
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 246 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Feb 2019to 1 Apr 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients with hematuria (macroscopic or microscopic)
Who cannot join
- history of Bladder Cancer
- history of pelvic irradiation,
- bleeding diathesis or receiving anticoagulants
- patients with upper urinary tract neoplasm or urolithiasis
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Bladder Cancer
- Being tested
- Cystoscopy, Computed tomography, DNA hypermethylation assay, Urine cytology
- Keywords
- Urothelial bladder carcinoma, Bladder cancer, Hematuria, Biomarkers, DNA methylation
- Medical subject headings
- Urinary Bladder Neoplasms, Hematuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CystoscopyProcedure or surgery
diagnostic cystoscopy for detection of any bladder lesions
Computed tomographyDiagnostic test
Computed tomography for patients to exclude bladder lesions
DNA hypermethylation assayGenetic
DNA hypermethylation assay of six genes (GATA4, P16, P14, APC, CDH1 and CD99)
Urine cytologyDiagnostic test
voided urine cytology for all patients
| Study group | Role | What they receive |
|---|---|---|
| Hematuria patients | Experimental | 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 Receives: Procedure: Cystoscopy; Diagnostic Test: Computed tomography; Genetic: DNA hypermethylation assay; Diagnostic Test: Urine cytology |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2022
- Study start1 Feb 2019
- Primary completion1 Jun 2021
- Study completion1 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Mansoura UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 246 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mansoura University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amr Abdel-Lateif El-Sawy, Mansoura University
- Investigators
- Amr A Elsawy, Principal investigator, Mansoura University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05362539
- Sponsor's protocol ID
- AS-4-2022
- Status last verified
- Apr 2022
- First submitted
- 27 Apr 2022
- Last updated
- 5 May 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Urine-Based DNA Methylation Biomarkers for Urothelial Bladder Carcinoma Detection in Patients With Hematuria
- ClinicalTrials.gov ID
- NCT05362539
- Acronym / sponsor ID
- AS-4-2022
- Conditions
- Bladder Cancer
- Keywords
- Urothelial bladder carcinoma, Bladder cancer, Hematuria, Biomarkers, DNA methylation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 246 participants (actual)
- Lead sponsor
- Mansoura UniversityUniversity, hospital or other
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Apr 2022 (actual)
- First posted
- 5 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hematuria patients | Experimental | Procedure: Cystoscopy, Diagnostic Test: Computed tomography, Genetic: DNA hypermethylation assay, Diagnostic Test: Urine cytologyVoided 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 |
Who may qualify
- Ages
- 18 years and older
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients with hematuria (macroscopic or microscopic)
Key exclusion criteria (4 listed)
- history of Bladder Cancer
- history of pelvic irradiation,
- bleeding diathesis or receiving anticoagulants
- patients with upper urinary tract neoplasm or urolithiasis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cystoscopydiagnostic cystoscopy for detection of any bladder lesions | Procedure or surgery | Hematuria patients |
| Computed tomographyComputed tomography for patients to exclude bladder lesions | Diagnostic test | Hematuria patients |
| DNA hypermethylation assayDNA hypermethylation assay of six genes (GATA4, P16, P14, APC, CDH1 and CD99) | Genetic | Hematuria patients |
| Urine cytologyvoided urine cytology for all patients | Diagnostic test | Hematuria patients |
Primary outcome
Rate of hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) in patients with urothelial bladder carcinoma
Time frame: 4 weeks
Rate of hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) in patients with urothelial bladder carcinoma
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amr A Elsawy principal investigator
Mansoura University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cystoscopy, Computed tomography and DNA hypermethylation assay in people with Bladder Cancer, run by Mansoura University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) in patients with urothelial bladder carcinoma (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2022.