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

NCT ID: NCT06741293

Last Updated: 2024-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

30000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-11-28

Study Completion Date

2029-11-28

Brief Summary

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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.

Detailed Description

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This study will analyse the gut microbiome in stool samples collected from individuals living in the Lisbon Metropolitan Area, Portugal. Using shotgun metagenomics, the investigators aim to identify microbiome biomarkers associated with the early detection of CRC and the progression of precancerous lesions (adenomas). The identified biomarkers will be tested to develop a non-invasive and highly sensitive screening tool for CRC and precancerous lesions.

Primary Objective:

To identify gut microbiome biomarkers in faecal DNA associated with CRC and/or high-risk adenomas.

Secondary Objectives:

i) Establish the correlation between FIT results, faecal microbiome testing and colonoscopy results.

ii) Estimate the incidence of CRC in the Lisbon Metropolitan Area among individuals aged 40-74 years, stratified by sex and age group.

iii) Analyse associations between clinical data (e.g., clinical history, lifestyle, and dietary habits), faecal microbiome profiles, FIT results, and colonoscopy outcomes, comparing individuals with CRC and/or high-risk adenomas against healthy individuals, for the total sample and by sex and age group; iv) Identify risk factors (e.g., clinical history, lifestyle, dietary habits) associated with CRC development, stratified by sex and age group.

Study Design:

This is an observational, prospective, longitudinal study involving individuals aged 40-74 years residing in the Lisbon Metropolitan Area who voluntarily enrol in the study.

Participants meeting all inclusion criteria and no exclusion criteria (as detailed in the relevant section) will be included. Based on sample size calculations using the Neyman allocation formula and taking as a reference the distribution of the population living in the Lisbon Metropolitan Area (stratified by sex and age groups: 40-49, 50-59, 60-64, 65-69 and 70-74 years), along with assumptions of the overall FIT test prevalence and sensitivity, a total of 30.000 participants will be enrolled.

At baseline, participants will provide a faecal sample within 2 to 10 days of enrolment. Demographic, clinical, and lifestyle data-including age, family history of CRC, personal medical history, smoking habits, physical activity levels, stress, and body mass index (BMI)-will be collected via self-administered questionnaires. Dietary habits and adherence to the Mediterranean diet will be assessed through telephone interviews.

Participants will be followed for six years, with faecal samples collected every 2 years. Clinical and lifestyle data will also be updated every two years throughout the study period.

Conditions

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Colorectal Cancer Screening Colorectal Cancer (CRC) Microbiome

Keywords

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colorectal cancer microbiome colorectal cancer screening biomarkers metagenomics

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Control group

Healthy participants with a negative colonoscopy result

No intervention: observational study

Intervention Type OTHER

No intervention: observational study

Colorectal cancer

Participants with colorectal cancer diagnosis confirmed by colonoscopy

No intervention: observational study

Intervention Type OTHER

No intervention: observational study

Low-risk polyps

Participants with positive colonoscopy and detection of low-risk adenomas

No intervention: observational study

Intervention Type OTHER

No intervention: observational study

High-risk polyps

Participants with positive colonoscopy and detection of high-risk adenomas

No intervention: observational study

Intervention Type OTHER

No intervention: observational study

Interventions

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No intervention: observational study

No intervention: observational study

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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
Minimum Eligible Age

40 Years

Maximum Eligible Age

74 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Hospital CUF Descobertas, Lisbon, Portugal

UNKNOWN

Sponsor Role collaborator

CUF Tejo Hospital

UNKNOWN

Sponsor Role collaborator

Hospital da Luz Lisboa, Portugal

UNKNOWN

Sponsor Role collaborator

Gulbenkian Institute for Molecular Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Gulbenkian Institute for Molecular Medicine

Lisbon, Lisbon District, Portugal

Site Status RECRUITING

Countries

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Portugal

Central Contacts

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Ana S Almeida, PhD

Role: CONTACT

Phone: +351 217999411

Email: [email protected]

Madalena Reis

Role: CONTACT

Phone: +351 217999411

Email: [email protected]

Facility Contacts

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Madalena Reis

Role: primary

Ana S Almeida, PhD

Role: backup

Related Links

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Other Identifiers

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101060102

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CAML Ref Nº: 111/23

Identifier Type: -

Identifier Source: org_study_id