Diagnostic Accuracy of a Panel of Bacterial Gene Markers (M3) for Colorectal Advanced Neoplasia

NCT ID: NCT05405673

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 2500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-06-29
• Study Completion Date: 2025-12-31

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.

Conditions

Colorectal Cancer; Colorectal Neoplasms; Colorectal Adenoma

Study Design

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

Study Groups

Colorectal neoplasia screening/surveillance cohort

Subjects with average risk of colorectal neoplasias requiring screening/surveillance colonoscopy

Fecal immunochemical test (FIT)

Intervention Type: DIAGNOSTIC_TEST

A kind of stool test

Interventions

Fecal immunochemical test (FIT)

A kind of stool test

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Bacterial gene marker test

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);

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dr Cipto Mangunkusumo General Hospital

OTHER

Sponsor Role: collaborator

Aster CMI Hospital

UNKNOWN

Sponsor Role: collaborator

Osaka International Cancer Institute

UNKNOWN

Sponsor Role: collaborator

Sano hospital

UNKNOWN

Sponsor Role: collaborator

Thingangyun Sanpya General Hospital

UNKNOWN

Sponsor Role: collaborator

Changi General Hospital

OTHER

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: collaborator

Phramongkutklao College of Medicine and Hospital

OTHER

Sponsor Role: collaborator

St. Mark's Hospital

UNKNOWN

Sponsor Role: collaborator

Oxford University Hospitals NHS Trust

OTHER

Sponsor Role: collaborator

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Louis Ho Shing Lau

Assistant Professor (clinical)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Prince of Wales Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Connie Seto

Role: CONTACT

waiyiseto@cuhk.edu.hk

6049 0760

Min Dai

Role: CONTACT

mindai@link.cuhk.hk

6049 0760

Facility Contacts

Louis Lau

Role: primary

Other Identifiers

2022.170

Identifier Type: -

Identifier Source: org_study_id