Unveiling the Microbial Impact on Intestinal Fibrosis

NCT ID: NCT06073288

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-11-01
• Study Completion Date: 2026-11-01

Brief Summary

Crohn's disease (CD), belonging to the class of Inflammatory Bowel Diseases, is a chronic inflammatory disorder that may affect any location of the gastrointestinal tract. It is characterized by transmural inflammation and an overwhelming immune response of the gut mucosa, which leads to severe clinical symptoms. More than 50% of CD patients develop a penetrating or stricturing disease due to fibrostenosis, which most of the time requires surgical intervention since no therapies have been found as effective yet. Among the histological features of stricturing CD, the thickening of the muscularis mucosae and muscularis propria is the main hallmark, primarily due to the excessive proliferation of mesenchymal cells and the increased accumulation of a collagen-rich extracellular matrix in the submucosa, caused by multiple mechanisms, including i) the proliferation of existing local fibroblasts, the induction of both ii) epithelial-to-, and iii) endothelial-to-mesenchymal transition. Even if the alteration of these mucosal functions is mainly caused by the continuous tissue injury occurring during CD-associated chronic inflammation, recent reports suggested that CD associated fibrosis may be driven by inflammation-independent triggers, such as microbiota dysbiosis.

Shedding the light on this aspect of CD fibrosis may lead to the development of innovative therapeutic strategies eventually blocking the gut thickening.

Detailed Description

This is a cross-sectional observational study involving patients with Crohn's Disease (CD) (n=15) and patients with non-Intestinal Bowel Disease (IBD) (n=5) undergoing surgery in the Gastroenterology and Digestive Endoscopy unit within Gastro Center (IRCCS Ospedale San Raffaele) according to the standard of care.

Specimens will be collected during the surgery, without other risks for the patients, since we will use only material left after pathologist analysis.

CD-derived surgical specimens will be processed to obtain a cell suspension, that will be frozen and stored for the following cell sorting. For non-IBD tissue processing, each surgical specimen will be cut into two pieces. One will be processed to obtain the cell suspension to be stored, whereas the remaining tissue will be processed to isolate lamina propria fibroblasts and endothelial cells, as well as to generate epithelial organoids.

Ospedale San Raffaele (OSR - Operative Unit (UO)1 (UO1)) is the promoter of this study. The other center participating in the study is University of Milan (UO2), which has in charge the development of 3D microfluidic devices for the in vitro experiments. Patients will be enrolled only in UO1.

Conditions

Crohn Disease

Study Design

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

Study Groups

Crohn's Disease (CD)

15 CD patients (5 patients/stage: (B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating).

Patient stratification is based on previous classifications done in accordance with the standard of care through TC, RMI or Ecography. For this reason, patients classification is known before surgery.

Surgical specimens of CD and no-IBD patients

Intervention Type: OTHER

Specimens of CD patients and patients without IBD-related disease (ex. diverticulitis) will be collected during the surgery, without other risks for the patients, since we will use only material left after pathologist analysis

non-Intestinal Bowel Disease patients (no-IBD)

5 patients without IBD-related diseases (ex. diverticulitis)

Surgical specimens of CD and no-IBD patients

Intervention Type: OTHER

Specimens of CD patients and patients without IBD-related disease (ex. diverticulitis) will be collected during the surgery, without other risks for the patients, since we will use only material left after pathologist analysis

Interventions

Surgical specimens of CD and no-IBD patients

Specimens of CD patients and patients without IBD-related disease (ex. diverticulitis) will be collected during the surgery, without other risks for the patients, since we will use only material left after pathologist analysis

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult patients ≥18 and <70 years
• All patients will sign the informed consent
• Given that it is an observational study, also pregnant and breastfeed patients could be included

Additionally, for CD patients:

• classification on different stages: (B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating). Patient stratification is based on previous classifications done in accordance with the standard of care through TC, RMI or Ecography.

Additionally, for non-IBD patients:

• subjects undergoing surgery for non-IBD diseases (ex. diverticulitis) in accordance with the standard of care

Exclusion Criteria

For CD patients:

• CD subjects without previously classification in B1, B2, B3
• Patients <18 years or > 70 years
• Patients without the signed informed consent

For non-IBD patients:

• Patients <18 years or > 70 years
• Patients without the signed informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Silvio Danese

Director of Gastroenterology and Endoscopy Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

IRCCS Ospedale San Raffaele

Milan, , Italy

Countries

Italy

Central Contacts

Federica Ungaro

Role: CONTACT

ungaro-federica@hsr.it

0226437864

Other Identifiers

RF-2021-12372637

Identifier Type: -

Identifier Source: org_study_id