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

NCT ID: NCT05144152

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-12-13
• Study Completion Date: 2025-06-15

Brief Summary

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.

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.

Conditions

Colorectal Adenoma; Advanced Adenoma; Colorectal Polyp

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

History of colorectal adenomas group

Subjects with known colorectal adenomas at the index colonoscopy

M3

Intervention Type: DIAGNOSTIC_TEST

A panel of four bacterial gene markers (Fn, m3, Ch and Bc)

FIT

Intervention Type: DIAGNOSTIC_TEST

faecal immunochemical test

Interventions

M3

A panel of four bacterial gene markers (Fn, m3, Ch and Bc)

Intervention Type: DIAGNOSTIC_TEST

FIT

faecal immunochemical test

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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);

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Louis Ho Shing Lau

Resident Specialist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Min Dai

Role: CONTACT

mindai@link.cuhk.edu.hk

+85260490760

Connie Seto

Role: CONTACT

waiyiseto@cuhk.edu.hk

+85260490760

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Other Identifiers

2021.558

Identifier Type: -

Identifier Source: org_study_id