Clinical trial NCT06720961: The Microbial Impact on Intestinal Fibrosis and the Associated Immune Microenvironment in Crohn's Disease
Official title: Unveiling the Microbial Impact on Intestinal Fibrosis and the Associated Immune Microenvironment: New Insights for the Pathogenesis and Treatment of Crohn's Disease-associated Complications
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Crohn Disease (CD)
Keywords: Crohn Disease
Fibrosis
Dysbiosis
Microbiota
Fibrostenosis
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: University of Florence
name: Humanitas Research Hospital IRCCS, Rozzano-Milan
name: Ministero dell'Istruzione, dell'Università e della Ricerca
name: Università Vita-Salute San Raffaele (MI)
First posted: 2024-12-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We will enroll 15 CD patients and 5 patients without IBD-related diseases (ex. diverticulitis) undergoing surgery according to the normal clinical practice for a total of 20 patients as following:

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

Patients will be stratified according to CT, MRI or ultrasound analysis (stratification already known before surgery)

- 5 patients without IBD-related diseases (e.g. diverticulitis)

All patients will be recruited only from San Raffaele Hospital (OSR). The participation is voluntary and the patient is allowed to refuse further participation in the protocol whenever he/she wants.

Participation in the study will not change the diagnostic-therapeutic treatment that patients undergo following the clinical practice, since patients will continue to be treated in accordance with clinical practice regardless of the results of this study.

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.

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

Primary outcomes:
measure: To identify the cellular subtypes and molecular pathways impacted by the specific bacterial factors during CD-associated fibrosis.
timeFrame: Experiments and analysis: 11th to 36th month
Secondary outcomes:
measure: To unravel the cellular and molecular mechanisms and dynamics induced by the bacterial factors in 3D models of intestinal fibrosis
timeFrame: Experiments and analysis: 11th to 36th month
Other outcomes:
measure: To validate in vitro results in an animal model by assessing the role of microbial factors in inducing fibrosis in an entire organism. Moreover, we will provide a possible therapeutic approach with strong clinical implications in the future
timeFrame: Experiments on in-vivo models: 13th to 24th month
Locations:
city: Milan
country: Italy
facility: IRCCS San Raffaele
Study officials:
affiliation: IRCCS San Raffaele
name: Silvio Danese, PhD-MD
role: PRINCIPAL_INVESTIGATOR
References: