Clinical trial NCT05405673: Diagnostic Accuracy of a Panel of Bacterial Gene Markers (M3) for Colorectal Advanced Neoplasia
Official title: A Prospective Cross-sectional Multi-center Study to Assess the Diagnostic Accuracy of a Panel of Bacterial Gene Markers (M3) for Colorectal Advanced Neoplasia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Cancer
Colorectal Neoplasms
Colorectal Adenoma
Keywords: FIT
Bacterial gene marker
Colonoscopy
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Dr Cipto Mangunkusumo General Hospital
name: Aster CMI Hospital
name: Osaka International Cancer Institute
name: Sano hospital
name: Thingangyun Sanpya General Hospital
name: Changi General Hospital
name: National Taiwan University Hospital
name: Phramongkutklao College of Medicine and Hospital
name: St. Mark's Hospital
name: Oxford University Hospitals NHS Trust
First posted: 2022-06-06
Enrollment: 2500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with average risk of colorectal neoplsia requring screening/surveillance colonoscopy

Brief summary: The investigators aim to evaluate and compare the diagnostic accuracy of FIT and the novel panel of bacterial gene markers (Fn, m3, Ch and Bc) collectively named as M3, in detecting colorectal advanced neoplasia.

Detailed description: Colorectal cancer (CRC) is the one of the most common cancers in Hong Kong with more than 5,500 new cases annually. There is prevailing evidence of increasing trend of young onset CRC globally. Early detection and resection of pre-malignant colorectal neoplasia has shown to reduce CRC-related mortality.

Non-invasive stool tests including guaiac-based faecal occult blood tests (gFOBT) and faecal immunochemical tests (FIT) are the cornerstones of population-based CRC screening programmes. The major limitation of this widely used strategy is its unsatisfactory sensitivities for CRC (79%) and advanced adenomas (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 colorectal neoplasia is warranted.

Multitarget stool DNA test and faecal microbial DNA markers appear to be promising options for CRC screening. 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%). We hypothesized that the combination of these 4 bacterial gene markers (known as M3) is more sensitive than FIT in detecting colorectal advanced neoplasia.

Eligibility criteria: Inclusion Criteria:

1. They require elective colonoscopy for colorectal cancer screening or polyp surveillance, or investigation of symptoms (e.g. anemia, change of bowel habit, abdominal pain);
2. Aged ≥18 years old;
3. Written informed consent obtained.

Exclusion Criteria:

1. Contraindications to colonoscopy (e.g. perforation, intestinal obstruction, unstable cardiopulmonary status);
2. Contraindication to polyp resection (e.g. active gastrointestinal bleeding, uninterrupted anticoagulation or dual antiplatelets);
3. Known colorectal cancer or adenoma for staged procedure;
4. Previous colonic resection;
5. Personal history of colorectal cancer;
6. Personal history of polyposis syndrome;
7. Personal history of inflammatory bowel disease;
8. Known pregnancy or lactation;
9. Advanced comorbid conditions (defined as American Society of Anesthesiologists grade 4 or above);

Primary outcomes:
measure: Sensitivity of bacterial gene markers panel (M3)
timeFrame: 1 month
measure: Sensitivity of FIT/FOBT
timeFrame: 1 month
Secondary outcomes:
measure: Sensitivity of M3 for early-stage (stage 1) or invasive (stage 2-4) colorectal cancers
timeFrame: 1 month
measure: Sensitivity of FIT/FOBT for early-stage (stage 1) or invasive (stage 2-4) colorectal cancers
timeFrame: 1 month
measure: Sensitivity of FIT/FOBT for advanced adenomas
timeFrame: 1 month
measure: Sensitivity of M3 for advanced adenomas
timeFrame: 1 month
measure: Sensitivity of FIT/FOBT for all adenomas
timeFrame: 1 month
measure: Sensitivity of M3 for all adenomas
timeFrame: 1 month
measure: Sensitivity of FIT/FOBT for sessile serrated lesions (SSL)
timeFrame: 1 month
measure: Sensitivity of M3 for sessile serrated lesions (SSL)
timeFrame: 1 month
measure: Specificity
timeFrame: 1 month
measure: Positive predictive value (PPV)
timeFrame: 1 month
measure: Negative predictive value (NPV)
timeFrame: 1 month
measure: Overall diagnostic accuracy
timeFrame: 1 month
measure: Microbiota changes in subjects with adenomas or normal findings after polypectomy
timeFrame: 1 month
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
References: