The Microbial Impact on Intestinal Fibrosis and the Associated Immune Microenvironment in Crohn's Disease

NCT ID: NCT06720961

Last Updated: 2025-02-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-04-30
• Study Completion Date: 2027-01-31

Brief Summary

The goal of this study is to find out if there is a direct connection between an imbalance of gut bacteria and the development of scar tissue in the gut by identifying important bacterial proteins found in scarred gut tissue. Our aim is to identify which types of cells and biological processes are affected by these bacterial proteins in people with Crohn's Disease. We will also study how these bacterial proteins cause changes in 3D models of gut fibrosis.

Detailed Description

More than 50% of CD patients develop a penetrating disease or stenosis due to fibrostenosis, which in most cases requires surgery, as no effective therapies have yet been found. The disease leads to both structural and functional alterations of the intestinal mucosa. Although the functional alteration of the mucosa is mainly caused by the continuous tissue damage that occurs during the chronic inflammation associated with CD, recent studies have suggested that the fibrosis associated with CD may be driven by triggering factors independent of inflammation, such as dysbiosis of the microbiota. Our proposal aims to establish the causal link between gut dysbiosis and fibrosis by studying the role of key bacterial proteins present in fibrotic gut tissue.

This project will ultimately offer new molecular targets for the development of possible tailor-made antifibrotic treatments, with likely benefits for healthcare, as it will facilitate the management of severe CD, avoiding surgery and reducing SSN costs.

Conditions

Crohn Disease (CD)

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

CD Patients

CD patients with established diagnosis and additionally classified according to 3 stages: B1 (more inflammatory, non-stricturing), B2 (stricturing, non-penetrating) and B3 (stricturing and penetrating). Patients will be stratified on the basis of CT, MRI or ultrasound analysis (stratification already known before surgery)

Collection of surgical specimen

Intervention Type: PROCEDURE

Specimens of CD patients and non-IBD related patients will be collected during the surgery performed for clinical practice, without other risks for the patients, since we will use only leftover material after pathologist analysis. All of the collected surgical samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed.

Collection of stool sample

Intervention Type: PROCEDURE

One week before the surgery to remove the stricture, fecal samples from CD patients belonging to B1, B2, B3 groups will be collected. They will be used for the exploratory objective. All of the collected fecal samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed.

Non-IBD Patients

Patients with other pathologies but not affected by IBD according to the previously reported clinical and endoscopic evaluation criteria (ex. diverticulitis)

Collection of surgical specimen

Intervention Type: PROCEDURE

Specimens of CD patients and non-IBD related patients will be collected during the surgery performed for clinical practice, without other risks for the patients, since we will use only leftover material after pathologist analysis. All of the collected surgical samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed.

Collection of stool sample

Intervention Type: PROCEDURE

One week before the surgery to remove the stricture, fecal samples from CD patients belonging to B1, B2, B3 groups will be collected. They will be used for the exploratory objective. All of the collected fecal samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed.

Interventions

Collection of surgical specimen

Specimens of CD patients and non-IBD related patients will be collected during the surgery performed for clinical practice, without other risks for the patients, since we will use only leftover material after pathologist analysis. All of the collected surgical samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed.

Intervention Type: PROCEDURE

Collection of stool sample

One week before the surgery to remove the stricture, fecal samples from CD patients belonging to B1, B2, B3 groups will be collected. They will be used for the exploratory objective. All of the collected fecal samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Adult patients ≥18 and <70 years
• Patients able to autonomously sign the informed consent
• Non pregnant or breastfeeding patients
• For CD patients: CD patients with established diagnosis and additionally classified according to 3 stages: B1 (more inflammatory, non-stricturing), B2 (stricturing, non-penetrating) and B3 (stricturing and penetrating). Patients will be stratified on the basis of CT, MRI or ultrasound analysis (stratification already known before surgery)
• For non-IBD patients: patients with other pathologies but not affected by IBD according to the previously reported clinical and endoscopic evaluation criteria (ex. diverticulitis)

Exclusion Criteria

• Patients <18 years or > 70 years
• Pregnant or breastfeeding patients
• For CD Patients: Subjects with CD who do not meet evaluation criteria described above
• For non-IBD patients: Patients undergoing anti-inflammatory and/or immunosuppressive treatments for IBD-related diseases

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Florence

OTHER

Sponsor Role: collaborator

Humanitas Research Hospital IRCCS, Rozzano-Milan

OTHER

Sponsor Role: collaborator

Ministero dell'Istruzione, dell'Università e della Ricerca

UNKNOWN

Sponsor Role: collaborator

Università Vita-Salute San Raffaele (MI)

UNKNOWN

Sponsor Role: collaborator

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Silvio Danese

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Silvio Danese, PhD-MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS San Raffaele

Locations

IRCCS San Raffaele

Milan, Italy, Italy

Countries

Italy

Central Contacts

Silvio Danese, PhD.-MD

Role: CONTACT

danese.silvio@hsr.it

+39 0226432807

Federica Ungaro, PhD.

Role: CONTACT

ungaro.federica@hsr.it

+39 0226437864

Facility Contacts

Federica Ungaro, PhD.

Role: primary

ungaro.federica@hsr.it

+39 0226437864

Francesco Fiorio

Role: backup

fiorio.francesco@hsr.it

+39 0226437159

Other Identifiers

Bando MUR 2022 PRIN-2022RKE4L

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PRIN-2022RKE4L

Identifier Type: -

Identifier Source: org_study_id