Improving Colorectal Cancer Early Screening in Portugal: Identification of Gut Microbiome Biomarkers in Stool (GUTBIOME-PT)

NCT06741293 | Recruiting

• 2 other identifiers: CAML Ref Nº: 111/23101060102
• Study Type: observational
• Target: 30,000
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer (CRC) is a major public health problem, responsible for 2 million new cases and almost 1 million deaths annually worldwide. In Portugal, as of 2022, CRC is the most common cancer, with 10,575 new cases reported, and the second leading cause of cancer-related mortality, accounting for 4,809 deaths (approximately 14% of all cancer-related deaths). In recent years, there has been an alarming increase in the incidence and mortality of CRC in people \<50 years of age. Early detection is crucial, as survival rates decline sharply from 90% when detected early to just 10% in advanced stages. Non-invasive diagnostic tests, such as the Faecal Immunochemical Test (FIT), have a low sensitivity for early-stage lesions and a high rate of false positives. Therefore, there is an urgent need to improve non-invasive diagnostic methods for the early detection of CRC, as effective screening can prevent it by detecting and removing premalignant lesions. Recent studies suggest that an altered gut microbiota may confer susceptibility to certain types of cancer. Interestingly, the gut microbiota of patients with adenomas or CRC differs from that of healthy individuals. This study aims to identify gut microbiome biomarkers in faecal samples associated with CRC and/or high-risk adenomas to improve early detection.

Conditions

Colorectal Cancer Screening; Colorectal Cancer (CRC); Microbiome

Keywords

colorectal cancer; microbiome; colorectal cancer screening; biomarkers; metagenomics

Outcome Measures

Primary Outcomes (2)

• Microbiome biomarkers associated with CRC and/or high-risk polyps.

  The faecal microbiota composition and gene profiles will be analysed using shotgun metagenomic sequencing on a subset of participants (up to 10,000 samples). Data will be integrated with lifestyle, dietary factors and colonoscopy results to identify biomarkers linked to CRC and adenomas.

  Baseline and Follow-up every 2 years up to 6 years

• Correlation between microbiome biomarkers and FIT results

  Faecal microbiome analysis results will be compared with FIT test results to evaluate the predictive value, negative predictive value, and overall effectiveness in detecting CRC in an asymptomatic population.

  Baseline and Follow-up every 2 years up to 6 years

Secondary Outcomes (6)

• Effect of diet on CRC risk and gut microbiota composition

  Baseline

• Effect of the Mediterranean Diet on CRC risk and gut microbiota composition

  Baseline

• Effect of physical activity on CRC risk and gut microbiota composition

  Baseline

• Effect of sleeping habits on CRC risk and gut microbiota composition

  Baseline

• Effect of stress levels on CRC risk and gut microbiota composition

  Baseline

Study Arms (4)

Control group

Healthy participants with a negative colonoscopy result

Other: No intervention: observational study

Colorectal cancer

Participants with colorectal cancer diagnosis confirmed by colonoscopy

Other: No intervention: observational study

Low-risk polyps

Participants with positive colonoscopy and detection of low-risk adenomas

Other: No intervention: observational study

High-risk polyps

Participants with positive colonoscopy and detection of high-risk adenomas

Other: No intervention: observational study

Interventions

No intervention: observational study OTHER

No intervention: observational study

Colorectal cancer; Control group; High-risk polyps; Low-risk polyps

Eligibility Criteria

• Age: 40 Years - 74 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Two different recruiting strategies will be used: * Opportunistic recruitment: recruitment will be conducted in collaboration with the gastroenterology and general medicine departments of partner hospitals in Lisbon. Eligible individuals scheduled for a screening colonoscopy will be informed about the study by an on-site study coordinator. Those willing to participate will sign an informed consent form. * Random recruitment: interested individuals can access detailed information and assess their eligibility by completing an online questionnaire on the study's website. Eligible participants can register and provide informed consent digitally. After registration, participants will be contacted to arrange the delivery of a self-collection kit for stool sample collection.

You may qualify if:

• Ability to provide written informed consent and comply with study procedures
• Reside in the Lisbon Metropolitan Area,, Portugal
• Age from 40 to 74 years

You may not qualify if:

• Age \< 40 years or ≥ 75 years
• Unable to provide informed consent
• Refusal to provide stool samples
• Active oncological disease
• Personal history of CRC
• Personal history of colon adenomas removed in the last 24 months
• First-degree family history of CRC
• Previous diagnosis of inflammatory bowel disease (ulcerative colitis, Crohn's disease or indeterminate colitis), inflammatory bowel syndrome, persistent and infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhoea of unknown aetiology or recurrent infection by Clostridioides difficile
• Severe cardiovascular or heart diseases with medical diagnosis
• Severe renal failure requiring hemodialysis
• Severe lung disease
• Pregnancy

Sponsors & Collaborators

• Gulbenkian Institute for Molecular Medicine: lead
• Hospital CUF Descobertas, Lisbon, Portugal: collaborator
• CUF Tejo Hospital: collaborator
• Hospital da Luz Lisboa, Portugal: collaborator

Study Sites (1)

Gulbenkian Institute for Molecular Medicine

Lisbon, Lisbon District, 1649-028, Portugal

RECRUITING

Related Links

• Public study website

Biospecimen

Retention: SAMPLES WITH DNA

Faecal samples with DNA - Participants will self-collect stool samples using a home collection kit into two tubes: one for FIT testing and the other for microbiome sequencing. Stool samples will be transported to the laboratory within 48 hours. FIT testing will be performed on its designated stool sample, while the samples for faecal microbiome sequencing will be subdivided into aliquots and stored at -80°C for subsequent 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

Central Study Contacts

Ana S Almeida, PhD

CONTACT

+351 217999411; ana.almeida@gimm.pt

Madalena Reis

CONTACT

+351 217999411; madalena.reis@gimm.pt

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: December 18, 2024
• Study Start: November 28, 2023
• Primary Completion: November 28, 2025
• Study Completion (Estimated): November 28, 2029
• Last Updated: December 18, 2024

Record last verified: 2024-12

Locations

PT (1)