DYNAMICS-LYNCH：DNA Methylation Analysis in Stool for Screening of Lynch Syndrome-Associated Colorectal Cancer

January 13, 2025 updated by: Pei-Rong Ding, Sun Yat-sen University

DNA Methylation Analysis in Stool Samples for Screening of Lynch Syndrome-Associated Colorectal Cancer

Colorectal cancer (CRC) has high incidence and mortality rates globally. Over 1 million new cases are diagnosed annually, and about 600,000 people die from the disease each year. In China, CRC ranks third in incidence and fifth in mortality. Its rates are rising due to lifestyle changes and an aging population.

Around 30% of CRC cases have a hereditary component, including familial adenomatous polyposis (FAP) and Lynch syndrome. Lynch syndrome, or hereditary non-polyposis colorectal cancer (HNPCC), accounts for 3%-5% of CRC cases. Early diagnosis, screening, and prophylactic surgery can reduce CRC mortality by 7%-42%, and mortality from endometrial and ovarian cancers by 1%-6%. Intensive screening is essential for Lynch syndrome patients, who are at high risk for CRC.

Due to the lack of early symptoms, many CRC cases are diagnosed in later stages, causing financial strain on patients, families, and society. Screening is an effective tool in reducing CRC-related mortality by more than 50%. In developed countries such as the U.S., U.K., and Japan, CRC screening is integrated into public health programs, emphasizing its role in prevention.

In China, CRC screening mainly involves the fecal occult blood test followed by colonoscopy, but this method faces challenges. First, the fecal occult blood test lacks sufficient sensitivity, leading to underdiagnosis. Second, colonoscopy is invasive with low patient acceptance. It also requires specialized facilities, advanced equipment, and skilled endoscopists, limiting its accessibility. Given China's large population and limited healthcare resources, universal colonoscopy screening is challenging, resulting in low screening rates.

To address these challenges, we propose replacing part of colonoscopy screening with DNA methylation testing of fecal samples. Self-sampling methylation screening could ease the strain on healthcare resources and improve patient compliance. By combining methylation screening with colonoscopy, we aim to reduce colonoscopy frequency and enhance overall compliance.

This study will include three rounds of methylation screening with colonoscopy as the control, involving 400 Lynch syndrome patients. The goal is to develop new screening criteria for this high-risk group, reduce colonoscopy frequency, and ultimately lower CRC incidence in Lynch syndrome patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet 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

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.

Detailed Description

Colorectal cancer (CRC) is a malignant disease with a high incidence and mortality rate worldwide. Globally, more than 1 million new cases of CRC are diagnosed annually, and approximately 600,000 patients die from the disease each year. In China, CRC has the third-highest incidence, following lung and stomach cancers and the fifth-highest mortality rate. With changes in lifestyle and an aging population, the incidence and mortality rates of CRC in China have been continuously rising. About 30% of colorectal cancer (CRC) patients exhibit a hereditary predisposition, including familial adenomatous polyposis (FAP) and Lynch syndrome. Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common hereditary colorectal cancer, accounting for 3%-5% of CRC cases. Several clinical criteria, such as the Amsterdam Criteria and Bethesda guidelines, are applied to the diagnosis of Lynch syndrome. Effective diagnosis, screening, and prophylactic surgery for Lynch syndrome can significantly reduce colorectal cancer mortality by 7%-42%, as well as mortality from endometrial and ovarian cancers by 1%-6%. Intensive screening measures are critical for patients with Lynch syndrome, who are considered to be at high-risk for CRC.

Due to the lack of early symptoms, many CRC patients are diagnosed at the middle to late stages of the disease, which places significant financial pressure not only on the patients themselves but also on society and their families. Screening is one of the most effective tools for preventing colorectal cancer and can reduce mortality by more than 50%. In developed countries such as the United States, the United Kingdom, and Japan, colorectal cancer screening has been integrated into public health programs, highlighting its critical role in disease prevention. Currently, colorectal cancer screening relies on the fecal occult blood test, followed by detailed examinations such as colonoscopy in our country, which still presents several challenges. First, the sensitivity of the fecal occult blood test is insufficient, leading to a high rate of underdiagnosis. Second, colonoscopy is an invasive procedure with relatively low acceptance among patients. Furthermore, colonoscopy is typically performed in a facility-based setting, which requires advanced endoscopic equipment and experienced endoscopists, making it highly dependent on medical resources. Given the limited healthcare resources, achieving universal coverage of the entire population with a facility-centered colonoscopy model is challenging, resulting in a low overall screening rate. Improvements are needed to enhance the efficiency and coverage of screening programs to better prevent and control the incidence of CRC. For patients with Lynch syndrome, intensive colonoscopy may lead to poor compliance due to its tedious process. To address these challenges, we propose to replace part of the colonoscopy screening with DNA methylation testing for fecal samples. Self-sampling methylation screening for colorectal cancer in patients with Lynch syndrome could not only alleviate the excessive strain on healthcare resources but also improve patient compliance with screening.

To explore the optimal screening strategy, reduce the frequency of colonoscopy, and improve patient compliance, we propose conducting methylation screening alongside colonoscopy for patients with Lynch syndrome. This study will include three consecutive rounds of head-to-head methylation screening, with colonoscopy as the control, involving 400 patients with Lynch syndrome. We aim to identify new screening criteria for this high-risk group, reduce the frequency of colonoscopy, improve screening compliance, and ultimately reduce the incidence of colorectal cancer in these patients.

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.
Observational

Enrollment (Estimated)

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.
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

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.

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients attending Sun Yat-sen University Cancer Center

Description

Inclusion Criteria:

  • Informed consent: patients are required to participate voluntarily and sign an informed consent form in writing；Patients diagnosed with Lynch syndrome；Agree to collect and send stool specimens for methylation sequencing as required；Willingness to undergo long-term follow-up and three rounds of methylation screening

Exclusion Criteria:

  • Patients with confirmed familial adenomatous polyposis or other hereditary colorectal cancers that are not Lynch syndrome；Patients who are unable to obtain a fecal specimen or whose specimen is substandard for follow-up testing；Patients diagnosed with colorectal cancer or currently undergoing surgery；Failure to sign informed consent

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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.
Patients with lynch syndrome
Patients diagnosed with Lynch syndrome by genetic testing
Diagnostic test: fecal DNA methylation testing
Three rounds of screening were performed. In the first year, colonoscopy was conducted along with concurrent fecal DNA testing performed prior to the colonoscopy. In the second year, fecal DNA testing was performed only if no polyps were detected during the colonoscopy in the first year; otherwise, both colonoscopy and fecal DNA testing were conducted. In the third year, a colonoscopy was performed with concurrent fecal DNA testing conducted before the procedure

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
Receiver Operating Characteristic Curve
Time Frame: From enrollment to the end of test at 3years
Area Under the Curve（AUC）
From enrollment to the end of test at 3years

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.
Sun Yat-sen University

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 (Estimated)

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.
January 10, 2025

Primary Completion (Estimated)

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.
June 30, 2028

Study Completion (Estimated)

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.
December 31, 2028

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).
January 10, 2025

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.
January 10, 2025

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.
March 25, 2025

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.
March 25, 2025

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.
January 13, 2025

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.
January 1, 2025

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.
  • 2024-FXY-142

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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