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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура 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.
• Процедура 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.

Первичные конечные точки

• To identify the cellular subtypes and molecular pathways impacted by the specific bacterial factors during CD-associated fibrosis. [Срок оценки: Experiments and analysis: 11th to 36th month]

Вторичные конечные точки (1)

• To unravel the cellular and molecular mechanisms and dynamics induced by the bacterial factors in 3D models of intestinal fibrosis [Срок оценки: Experiments and analysis: 11th to 36th month]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Италия · 1 центр

• IRCCS San Raffaele — Milan

Идентификаторы

NCT: NCT06720961 · PRIN-2022RKE4L · Bando MUR 2022 PRIN-2022RKE4L

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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