Clinical trial NCT06502704: Bile Acids and Microbiome in Early Colorectal Carcinogenesis
Official title: Bile Acids and Microbiome - Possible Novel Progression Factors and Diagnostic Indicators in Early Colorectal Carcinogenesis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Neoplasms
Colorectal Cancer
Colorectal Polyp
Microbiome
Bile Acid Malabsorption
Keywords: Colorectal Neoplasms
Colorectal Cancer
Colorectal Polyp
Microbiome
Bile Acid
Lead sponsor: Vilnius University
Sponsor class: OTHER
Collaborators: name: Vilnius University Hospital Santaros Klinikos
First posted: 2024-07-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: \> 18 years of age, atients that have clinical indications for colonoscopy.

Brief summary: Currently colorectal cancer pathogenesis is mainly explained by the adenoma-carcinoma sequence theory that was proposed more than half a century ago. It mainly focuses on the explanation of genetic mutations that develop throughout the disease course. However, several studies argue that there are also noticeable bile acid metabolism changes and microbiome composition changes within in colorectal cancer patients. However, carcinoma is the final step in the sequence, and prior steps are noticeably less well studied. Thus, the investigators hypothesize, that changes within microbiome and the changes in the urine, serum and gut bile acid composition further leads to the development of colorectal adenoma and subsequent invasive carcinoma.

Adult participants (15 per group) referred for colonoscopy and histologically diagnosed with small (\<1cm) adenomas, large (\>1cm) adenomas, invasive CRC will be included in the study, as well as 15 healthy controls. Fecal samples will be collected from all participants before bowel preparation. Additionally, urine and serum samples will be collected. Participants will undergo polypectomy, endoscopic mucosal resections, depending on the location, size and histology of the polyp found. During colonoscopy the mucosal biopsy specimens from the lesion and from the healthy bowel -terminal ileum, and colon will be obtained using sterile biopsy forceps. The collected samples will be stored for bile acid and microbiome analysis and for possible further pathology and genetic testing. Healthy participants without visible colorectum pathology during colonoscopy will undergo colon and terminal ileum mucosal sampling.

The investigators plan to evaluate the correlation between the urine and gut microbiome changes and bile acid composition and concentration in adenoma-carcinoma sequence and possibly determine novel bile acids. In addition, fecal, urine and tissue samples will be explored for gut microbiota and bile acid composition changes in healthy and along the adenoma-carcinoma sequence, with the possibility to propose a diagnostic test.


Eligibility criteria: Inclusion Criteria:

- Patients that have clinical indications for colonoscopy

Exclusion Criteria:

* Pregnancy
* Immunocompromised
* Previously diagnosed colorectal diseases
* Radiotherapy to the pelvis
* Long term antibiotic use within 6 months
* Continuous use of proton pump inhibitors

Primary outcomes:
measure: Microbiome and bile acid composition correlation to dysplastic changes
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Bile acid composition in healthy participants
timeFrame: Through study completion, an average of 2 years
measure: Bile acid composition in urine, stool and serum
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
Study officials:
affiliation: Vilnius University
name: Tomas Poskus, PhD
role: PRINCIPAL_INVESTIGATOR
References: