Diagnostic Accuracy of M3 in Predicting Colorectal Advanced Adenoma Recurrence (M3-AA) (M3-AA)

August 26, 2024 updated by: Louis Ho Shing Lau, Chinese University of Hong Kong

A Prospective Study to Assess the Diagnostic Accuracy of a Panel of Bacterial Gene Markers (M3) in Predicting Colorectal Advanced Adenoma Recurrence

The investigators aim to evaluate the diagnostic accuracy of FIT and the novel panel of four bacterial gene markers collectively named as M3, to detect recurrent advanced adenomas in patients with history of colonic adenomas.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Colorectal cancer (CRC) is the most common cancer in Hong Kong with more than 5,600 new cases annually. There is prevailing evidence of increasing trend of young onset CRC globally. Early detection and endoscopic resection of pre-malignant colonic adenomas has shown to reduce CRC-related mortality.

After the index colonoscopy, a surveillance colonoscopy will be required at regular intervals, depending on the number, size and histology of colonic polyps. Studies have reported the use of faecal immunochemical test (FIT) to reduce the burden on surveillance endoscopy service. However, approximately 30-40% of interval CRC and 40-70% of advanced adenomas (AA) could be missed by this strategy. The major limitation of this widely used non-invasive stool test is its unsatisfactory sensitivities for CRC (79%) and AA (40%). The sensitivity for non-advanced adenomas is even lower than 10%. A large proportion of advanced and non-advanced adenomas will be missed by FIT alone. Therefore, identification of alternative non-invasive test with better sensitivity to detect colonic adenomas is warranted.

Multitarget stool DNA test and faecal microbial DNA markers appear to be the most promising stool-based diagnostic biomarkers for screening CRC. Several bacterial gene markers have been identified by metagenome sequencing and reported to be associated with CRC, including Fusobacterium nucleatum (Fn), Clostridium hathewayi (Ch) and Bacteroides clarus (Bc). However, these molecular markers had low accuracy in distinguishing adenomas from normal tissue. Recently, a new Lachnoclostridium gene marker (labelled as 'm3') has been shown to have high diagnostic yield for the detection of colorectal adenomas. In a case-control study of 1012 subjects, a linear increasing trend of m3 level was observed from fecal samples of healthy subjects to those with adenomas and cancers. The overall sensitivity of m3 was significantly higher than FIT in detecting all adenomas (48% vs 9.3%), AA (50.8% vs 16.1%) and non-advanced adenomas (44.2% vs 0%). The diagnostic accuracy of m3 could be further enhanced by combining with a panel of fecal microbial markers composing of Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Clostridium hathewayi (Ch) for CRC (82.3%) and adenomas (64.2%). The combination of these 4 bacterial gene markers (known as M3) has recently been proven to be useful in detecting adenoma recurrence after polypectomy in a retrospective study. The hypothesis is that it would be effective in the detection of recurrent advanced adenomas.

This prospective cohort study aims to evaluate the diagnostic accuracy of FIT and the novel panel of four bacterial gene markers (Fn, m3, Ch and Bc) collectively named as M3, to detect recurrent advanced adenomas in patients with history of colonic adenomas.

Study Type

Observational

Enrollment (Estimated)

600

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

Study Locations

  • Hong Kong
    • New Territories
      • Shatin, New Territories, Hong Kong
        • Recruiting
        • Prince of Wales Hospital

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

Sampling Method

Non-Probability Sample

Study Population

Subeject with history of colorectal adenomas

Description

Inclusion Criteria:

  1. Known colorectal adenomas during index colonoscopy;
  2. Available baseline M3 and FIT results before index colonoscopy;
  3. Aged ≥18 years old;
  4. Written informed consent obtained.

Exclusion Criteria:

  1. Refusal or unfit to undergo surveillance colonoscopy;
  2. Incomplete colonoscopy, incomplete removal of colorectal adenomas, or inadequate bowel preparation (defined as Boston Bowel Preparation Scale score 0 or 1 in any colonic segment) at index colonoscopy;
  3. Previous colonic resection;
  4. Personal history of colorectal cancer;
  5. Personal history of polyposis syndrome;
  6. Personal history of inflammatory bowel disease;
  7. Known pregnancy or lactation;
  8. Advanced comorbid conditions (defined as American Society of Anesthesiologists grade 4 or above);

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: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
History of colorectal adenomas group
Subjects with known colorectal adenomas at the index colonoscopy
Diagnostic test: M3
A panel of four bacterial gene markers (Fn, m3, Ch and Bc)
Diagnostic test: FIT
faecal immunochemical test

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity of the panel of bacterial gene markers (M3) or FIT in detection of recurrent colonic advanced adenomas
Time Frame: 3 years
The proportion of subjects with true positive results of either M3 or FIT among those with one of more advanced adenomas detected during the surveillance colonoscopy examination at year 3
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity for advanced adenomas (year 3)
Time Frame: 3 years
The proportion of subjects with true positive results of either M3 or FIT among those with one of more advanced adenomas detected at year 3 colonoscopy
3 years
Sensitivity for non-advanced adenomas (year 3)
Time Frame: 3 years
The proportion of subjects with true positive results of either M3 or FIT among those with non-advanced adenomas detected at year 3 colonoscopy
3 years
Sensitivity for all adenomas (year 3)
Time Frame: 3 years
The proportion of subjects with true positive results of either M3 or FIT among those with all adenomas detected at year 3 colonoscopy
3 years
Specificity (year 3)
Time Frame: 3 years
Proportion of true negative results of M3/FIT among those with no adenoma detected in colonoscopy (year 3)
3 years

Collaborators and Investigators

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

Sponsor

Chinese University of Hong Kong

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)

December 13, 2021

Primary Completion (Estimated)

December 15, 2024

Study Completion (Estimated)

June 15, 2025

Study Registration Dates

First Submitted

November 21, 2021

First Submitted That Met QC Criteria

November 21, 2021

First Posted (Actual)

December 3, 2021

Study Record Updates

Last Update Posted (Actual)

August 27, 2024

Last Update Submitted That Met QC Criteria

August 26, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021.558

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to share individual participant data to other researchers

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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