Clinical trial NCT06741293: Improving Colorectal Cancer Early Screening in Portugal: Identification of Gut Microbiome Biomarkers in Stool (GUTBIOME-PT)
Official title: Improving Colorectal Cancer Early Screening in Portugal: Identification and Validation of Biomarkers of Gut Microbiome in Stool
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Cancer Screening
Colorectal Cancer (CRC)
Microbiome
Keywords: colorectal cancer
microbiome
colorectal cancer screening
biomarkers
metagenomics
Lead sponsor: Gulbenkian Institute for Molecular Medicine
Sponsor class: OTHER
Collaborators: name: Hospital CUF Descobertas, Lisbon, Portugal
name: CUF Tejo Hospital
name: Hospital da Luz Lisboa, Portugal
First posted: 2024-12-18
Enrollment: 30000
Sex: ALL
Minimum age (years): 40
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Microbiome biomarkers associated with CRC and/or high-risk polyps.
timeFrame: Baseline and Follow-up every 2 years up to 6 years
measure: Correlation between microbiome biomarkers and FIT results
timeFrame: Baseline and Follow-up every 2 years up to 6 years
Secondary outcomes:
measure: Effect of diet on CRC risk and gut microbiota composition
timeFrame: Baseline
measure: Effect of the Mediterranean Diet on CRC risk and gut microbiota composition
timeFrame: Baseline
measure: Effect of physical activity on CRC risk and gut microbiota composition
timeFrame: Baseline
measure: Effect of sleeping habits on CRC risk and gut microbiota composition
timeFrame: Baseline
measure: Effect of stress levels on CRC risk and gut microbiota composition
timeFrame: Baseline
measure: Risk factors (medical history, lifestyle and dietary habits) associated with CRC and/or high-risk polyps
timeFrame: Baseline and Follow-up every 2 years up to 6 years
Other outcomes:
Locations:
city: Lisbon
country: Portugal
facility: Gulbenkian Institute for Molecular Medicine
Study officials:
References: