Bile Acids and Microbiome in Early Colorectal Carcinogenesis

NCT06502704 | Recruiting

• 1 other identifier: 2024/5-1587-1047
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Neoplasms; Colorectal Cancer; Colorectal Polyp; Microbiome; Bile Acid Malabsorption

Keywords

Colorectal Neoplasms; Colorectal Cancer; Colorectal Polyp; Microbiome; Bile Acid

Outcome Measures

Primary Outcomes (1)

• Microbiome and bile acid composition correlation to dysplastic changes

  Microbiome and bile acid composition changes will be detected and correlated with progression of the dysplastic changes within the epithelium of the large bowel.

  Through study completion, an average of 2 years

Secondary Outcomes (2)

• Bile acid composition in healthy participants

  Through study completion, an average of 2 years

• Bile acid composition in urine, stool and serum

  Through study completion, an average of 2 years

Study Arms (4)

Control

No pathology upon colonoscopy

Small adenoma

\< 1cm size polyp upon colonoscopy

Large adenoma

\> 1cm size polyp upon colonoscopy

Cancer

Adenocarcinoma upon colonoscopy

Eligibility Criteria

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

Study Population

\> 18 years of age, atients that have clinical indications for colonoscopy.

You may qualify if:

• \- Patients that have clinical indications for colonoscopy

You may not qualify if:

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

Sponsors & Collaborators

• Vilnius University: lead
• Vilnius University Hospital Santaros Klinikos: collaborator

Study Sites (1)

Vilnius University Hospital Santaros Klinikos

Vilnius, 08661, Lithuania

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Fecal, Blood, Urine and gut biopsy samples

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

• Tomas Poskus, PhD

  Vilnius University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tomas Poskus, PhD

CONTACT

+37052365000; Tomas.Poskus@santa.lt

Matas Jakubauskas, PhD

CONTACT

+37052365000; Matas.Jakubauskas@santa.lt

Study Design

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

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: July 16, 2024
• Study Start: July 5, 2024
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

LI (1)