The Role of FAM19A4 and Hsa-mir-124 Methylation in Predicting Prognosis of Untreated Cervical Intraepithelial Neoplasia 2 (CIN 2)

November 14, 2022 updated by: University Medical Centre Maribor
High-risk precancerous cervical lesions are divided into stage 2 and 3 cervical intraepithelial neoplasia (CIN 2 and 3). CIN 3 represents a direct pre-stage of invasive cancer, has a high rate of progression and a high degree of agreement with the final histological diagnosis. In CIN 2 lesions, the rate of agreement with the final histological diagnosis is lower and the rate of spontaneous regression is higher. Due to the higher rate of regression and possible complications after excisional treatment, conservative active monitoring can be considered in selected young CIN 2 patients. A recent meta-analysis reported a high rate of spontaneous clinical regression of CIN 2, particularly in women under 30 years old. There are currently no prospectively validated prognostic biomarkers to determine which CIN 2 will progress to higher grade and which will regress to lower grade of change. Recent research has studied HPV methylation and microbiome analysis as biomarkers. A number of studies have shown that host cell DNA methylation levels in cervical scrapes increase with underlying cervical disease severity and are highest in cervical cancer. DNA methylation involves the covalent binding of a methyl group to the 5´ position of a cytosine molecule in CpG dinucleotides. Besides global hypomethylation, the overall loss of methylation during carcinogenesis, resulting in chromosomal instability, and the silencing of tumour suppressor genes by local hypermethylation of CpG-rich promoter regions contribute to cancer development. Gene promoter methylation can be easily accessed by sensitive, quantitative methylation-specific PCR providing an objective test outcome. The aim of this study was to determine the effect of the methylation rate of two suppressor genes- FAM19A4 and hsa-mir-124 on the rate of CIN 2 regression, persistence or progression in women younger than 36 years (≤35 years old).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Slovenia
      • Maribor, Slovenia, 2000
        • Recruiting
        • University Medical Centre Maribor
        • Contact:
          • Milena Miklus, MD

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 36 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologically confirmed CIN 2 (with biopsy of colposcopically suspicious changes in the cervix)
  • Age under 30 years
  • Satisfactory colposcopy (transformation zone fully visible)
  • Size of change below 75% of transformation zone
  • The change in the ectocervix is fully visible
  • Age 30-35 years, if the patient is non-smoker and the change in the cervix does not exceed 50% of the area of the transformation zone
  • Signing an informed consent to participate in the survey
  • Willingness to perform inspections every 6 months

Exclusion Criteria:

  • Age 36 years or older
  • Unsatisfactory colposcopy (transformation zone not fully visible)
  • Size of change exceeds 75% of the transformation zone
  • The change in the ectocervix is not completely visible
  • Age 30-35 years for smokers or if the change exceeds 50% of the area of the transformation zone
  • Suspicted glandular precancerous changes
  • Histologically verified CIN 2 with cytological changes of glandular cells
  • Colposcopically suspected invasive disease
  • Histologically verified CIN 2 and histologically verified AIS
  • Histologically verified CIN 2 and histologically verified invasive cancer elsewhere in the cervix
  • Refusal to sign participation in the survey
  • Unwillingness to perform control examinations
  • Weakness of an immune system
  • Cervical conization performed in the past
  • Treatment with local immunomodulators

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

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Women with CIN 2 and under 36 years old
We will analyze patients under 36 years old (≤ 35) with histological confirmed CIN 2 lesions and without any additional risk factors.
Diagnostic test: Testing DNA methylation test for predicting prognosis of untreated CIN 2
After being diagnosed with CIN 2, patients will first be contacted by telephone and invited to participate in the study. If patients agree to participate in the research, they will sign a consent to participate in the research. After that, we will perform a colposcopy and take a cervical swab for analysis with the QIAsure Methylation Test Kit (Qiagen, Gaithersburg, USA), which will determine the methylation of tumor suppressor genes FAM19A4 and has-mir-124. Patients will complete a questionnaire. The total duration of tracking in both groups will be two years. The QIAsure Methylation Test will be performed to analyze methylation. It is a methylation-specific PCR test that detects hypermethylation of the tumor promoter suppressor genes FAM19A4 and has-mir-124. The samples on which we will use this test are bisulfite-converted DNA obtained by triage test for high-risk HPV - Hybrid Capture 2 HPV DNA Test (hc2, Qiagen, Gaithersburg, USA).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Impact of the degree of methylation on progression of CIN 2
Time Frame: two years
The primary clinical outcome will be the effect of the degree of methylation on the progression of CIN 2 to CIN 3+ (CIN 3 and cervical cancer).
two years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Rate of progression of CIN 2
Time Frame: two years
The secondary clinical outcome will be the rate of progression of CIN 2 to CIN 3+, the rate of clinical decline to normal histological picture (˂ CIN 1) and the rate of persistence of precancerous change after two years (CIN 2 or persistent CIN 1).
two years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Medical Centre Maribor

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 22, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 22, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRP-2021/02-04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

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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