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

Recruiting

• Conditions: Advanced Adenoma; Colorectal Polyp; Colorectal Adenoma
• Interventions: Diagnostic Test: M3; Diagnostic Test: FIT

• Registration Number: NCT05144152
• Lead Sponsor: Chinese University of Hong Kong

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.

Study Timeline

• Study First Submitted: 2021-11-21
• Study First Submitted QC: 2021-11-21
• Study First Posted: 2021-12-03
• Study Start: 2021-12-13
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-26
• Last Update Posted: 2024-08-27
• Primary Completion: 2024-12-15
• Study Completion: 2025-06-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

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.

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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);

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
History of colorectal adenomas group	FIT	Subjects with known colorectal adenomas at the index colonoscopy
History of colorectal adenomas group	M3	Subjects with known colorectal adenomas at the index colonoscopy

Primary Outcome Measures

Name	Time	Method
Sensitivity of the panel of bacterial gene markers (M3) or FIT in detection of recurrent colonic advanced adenomas	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

Secondary Outcome Measures

Name	Time	Method
Sensitivity for advanced adenomas (year 3)	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
Sensitivity for non-advanced adenomas (year 3)	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
Sensitivity for all adenomas (year 3)	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
Specificity (year 3)	3 years	Proportion of true negative results of M3/FIT among those with no adenoma detected in colonoscopy (year 3)

Trial Locations

Locations (1)

Prince of Wales Hospital; 🇭🇰 Shatin, New Territories, Hong Kong