Clinical trial NCT05144152: Diagnostic Accuracy of M3 in Predicting Colorectal Advanced Adenoma Recurrence (M3-AA)
Official title: A Prospective Study to Assess the Diagnostic Accuracy of a Panel of Bacterial Gene Markers (M3) in Predicting Colorectal Advanced Adenoma Recurrence
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Adenoma
Advanced Adenoma
Colorectal Polyp
Keywords: FIT
Bacterial marker
Colonoscopy
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2021-12-03
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subeject with history of colorectal adenomas

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.

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);

Primary outcomes:
measure: Sensitivity of the panel of bacterial gene markers (M3) or FIT in detection of recurrent colonic advanced adenomas
timeFrame: 3 years
Secondary outcomes:
measure: Sensitivity for advanced adenomas (year 3)
timeFrame: 3 years
measure: Sensitivity for non-advanced adenomas (year 3)
timeFrame: 3 years
measure: Sensitivity for all adenomas (year 3)
timeFrame: 3 years
measure: Specificity (year 3)
timeFrame: 3 years
Other outcomes:
Locations:
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
Study officials:
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