A Non-invasive Gut Microbiome-based Diagnostic Tool for the Screening of Colorectal Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 1,006
- Locations
- 1
- Primary Endpoint
- Gut microbiome-based diagnostic tool for CRC and advanced colorectal adenomas detection
Study Overview
Brief Summary
Colorectal cancer (CRC) is one of the most common cancer and cause of cancer death worldwide. Population-based screening programs for average-risk populations have proven effective in reducing both incidence and mortality of CRC through early detection of cancer. The fecal immunochemical testing (FIT), has still a suboptimal diagnostic yield, with both missed adenomas and, mainly, unnecessary colonoscopies.The identification of novel, non-invasive biomarkers is currently one of the research areas driving most expenditure forces in the field of CRC.A large body of evidence shows that alterations of the gut microbiome and the enrichment of specific taxa(e.g. Fusobacterium nucleatum, Parvimonas micra, and others) are involved in the pathogenesis of CRC. Moreover, recent studies, have discovered common microbial signatures able to reproducibly discriminate between patients with CRC and healthy controls.
The goal of this observational study to develop a gut microbiome-based diagnostic tool for the identification of CRC and advanced colorectal adenomas in patients enrolled in the national colorectal cancer (CRC) screening program (50-74 years old) and among who refer to all centers involved in this study for screening colonoscopy with positivity of FIT, of both sex.
The primary endpoint of the study is to develop a gut microbiome-based diagnostic tool for the identification of CRC and advanced colorectal adenomas in patients involved in the national CRC screening program at 30 months, using both statistical and machine learning approaches
The secondary endpoints are:
- The association of clinical and colonoscopy outcomes with FIT results at 30 months
- The characterization of gut microbiome from an ecological, taxonomic, phylogenetic and functional point of view at 30 months
- The association between microbiome signatures with clinical and colonoscopy outcomes at 30 months, through statistical and machine-learning algorithms At baseline, enrolled patients will provide a fecal sample within 2 weeks from enrollment and demographic, clinical characteristics and laboratory data will be recorded. Enrolled patients will be scheduled for colonoscopy, as for clinical practice, within 4 weeks from the positive FIT and histology of resected lesions will be assessed by experienced pathologists according to the WHO classification and the Vienna criteria.
Clinical, endoscopic and microbial data will be combined through statistical and machine learning algorithms to identify specific microbial biomarkers associated with CRC and develop a new diagnostic tool, based on a scoring system.
This tool will be validated, and its diagnostic performances will be compared with traditional screening methods.
Detailed Description
Colorectal cancer (CRC) is the 3rd most common cancer and the 2nd most common cause of cancer death worldwide, with nearly 2 million new cases and one million deaths in 2020. In the last decades, a population-based screening programs for average-risk populations have established as an effective strategy to reduce both incidence and mortality of CRC through early detection of cancer. The fecal immunochemical testing (FIT), the reference diagnostic tool in most countries, has still a suboptimal diagnostic yield, with both missed adenomas and, mainly, unnecessary colonoscopies. For these reasons, in the last years the identification of novel, non-invasive biomarkers is absolutely advocatein the field of CRC. A large body of evidence shows that alterations of the gut microbiome and the enrichment of specific taxa (e.g. Fusobacterium nucleatum, Parvimonas micra, and others) are involved in the pathogenesis of CRC. Moreover, recent studies, including metagenomic meta-analyses from our group, have discovered common microbial signatures able to reproducibly discriminate between patients with CRC and healthy controls. Based on this evidence, international guidelines have recently advocated the exploitation of microbiome-based biomarkers for the screening of CRC in clinical practice, but such studies are not yet available to date.
The primary objective is to develop a gut microbiome-based diagnostic tool for the identification of CRC and advanced colorectal adenomas.
The secondary objectives are:
- To associate FIT with clinical and colonoscopy outcomes
- To characterize gut microbiome of enrolled patients
- To associate microbiome signatures with clinical and colonoscopy outcomes
This is an observational prospective multicenter study, in which patients will be selected among those enrolled in the national colorectal cancer (CRC) screening program and among who refer to all centers involved in this study for screening colonoscopy.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 50 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients participating in the national CRC screening program (50-74 years old)
- •Positivity to the FIT;
- •Ability to provide written informed consent and to be compliant with the study procedures
Exclusion Criteria
- •Patients unfit for colonoscopy;
- •Other oncological conditions;
- •Concomitant severe comorbidities or gastrointestinal (GI) organic diseases (e.g. diverticular disease, inflammatory bowel disease);
- •Antibiotics,proton pump inhibitors or probiotics within 4 weeks prior to enrollment.
Arms & Interventions
Study cohort consists of patients enrolled in the national colorectal cancer (CRC) screening program
Participants will be selected among those enrolled in the national colorectal cancer (CRC) screening program and among who refer to all centers involved in this study for screening colonoscopy. Patients with all inclusion criteria and none of the exclusion criteria will be considered for this study. A total of n = 612 subjects will be enrolled. More specifically, 502 patients will be enrolled based on the updated sample size calculation. An additional 10 patients will be enrolled to account for a potential 2% dropout rate, as observed during the study conduct.
Moreover, an independent validation cohort of 100 patients (approximately 20% of the main study cohort) will be enrolled to allow rigorous internal validation of the identified biomarkers and diagnostic models. Patients enrolled in the validation cohort will meet the same inclusion and exclusion criteria as the main study population and will undergo the same study procedures.
Intervention: Gut microbiome testing (Diagnostic Test)
Outcomes
Primary Outcomes
Gut microbiome-based diagnostic tool for CRC and advanced colorectal adenomas detection
Time Frame: 30 months
The development of a gut microbiome-based diagnostic tool for the identification of CRC and advanced colorectal adenomas in patients involved in the national CRC screening program, using both statistical and machine learning approaches
Secondary Outcomes
- Association between clinical and endoscopic outcomes with FIT(30 months)
- Microbiome characteristics of fecal samples(30 months)
- Association between microbiome signatures with clinical and endoscopic outcomes(30 months)
Investigators
IANIRO GIANLUCA
Principal Investigator, MD, PhD
Fondazione Policlinico Universitario Agostino Gemelli IRCCS