Microbiome Testing for the Screening of Colorectal Cancer

NCT06588166 | Recruiting

• 2 other identifiers: 6902PNRR-POC-2023-12377319
• Study Type: observational
• Target: 1,006
• Locations: 1 country
• Sites: 1

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 24 months, using both statistical and machine learning approaches The secondary endpoints are:

• The association of clinical and colonoscopy outcomes with FIT results at 24 months
• The characterization of gut microbiome from an ecological, taxonomic, phylogenetic and functional point of view at 24 months
• The association between microbiome signatures with clinical and colonoscopy outcomes at 24 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.

Conditions

Colorectal Cancer

Keywords

microbiome; microbiome testing; colorectal cancer; colorectal cancer screening

Outcome Measures

Primary Outcomes (1)

• Gut microbiome-based diagnostic tool for CRC and advanced colorectal adenomas detection

  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

  24 months

Secondary Outcomes (3)

• Association between clinical and endoscopic outcomes with FIT

  24 months

• Microbiome characteristics of fecal samples

  24 months

• Association between microbiome signatures with clinical and endoscopic outcomes

  24 months

Study Arms (1)

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. In this cohort 1006 patients will be enrolled (838 patients by sample size + 168 patients as validation cohort)

Diagnostic Test: Gut microbiome testing

Interventions

Gut microbiome testing DIAGNOSTIC_TEST

Gut microbiome testing for the characterization of the patient gut microbiome

Study cohort consists of patients enrolled in the national colorectal cancer (CRC) screening program

Eligibility Criteria

• Age: 50 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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=1006 subjects will be enrolled. More specifically, 838 patients will be enrolled based on sample size calculation and to cover a 10% dropout risk. Moreover, an additional cohort of 168 patients (20% of the total) will be enrolled to be used as an internal validation set for rigorous validation of the identified biomarkers. Patients enrolled in this validation cohort will have the same exclusion and inclusion criteria of other patients, and will undergo the same study procedures.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Agostino Gemelli, IRCCS

Roma, 00168, Italy

RECRUITING

Related Publications (15)

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Biospecimen

Retention: SAMPLES WITH DNA

For each patient enrolled a stool samples will be collected, using a Zymo buffer, to preserve feces at room temperature for up to 48 hours. Fecal samples will be stored at -80°C and will be used for shotgun metagenomics analysis.

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Gianluca Ianiro, MD, PhD

  Fondazione Policlinico Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gianluca Ianiro, MD, PhD

CONTACT

0630159539; gianluca.ianiro@unicatt.it

Serena Porcari, MD, PhD

CONTACT

0630159539; serena.porcari@guest.policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD, PhD

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: September 19, 2024
• Study Start: November 29, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available after the completion of the study, for 5 years
• Access Criteria: Data will be given upon reasonable request to the PI

Locations

IT (1)