Spatially and Temporally Resolving Predictive Biomarkers of Postoperative Recurrence and Complications in Chronic Intestinal Inflammation

Recruiting

• Conditions: Ulcerative Colitis; Crohn Disease
• Interventions: Procedure: UC patients; Procedure: CD patients

• Registration Number: NCT06516341
• Lead Sponsor: IRCCS Ospedale San Raffaele

Brief Summary

A portion of patients with Inflammatory bowel disease often require surgical intervention since they do not respond to the current therapies. Besides this risk, patients may develop post-operative disease complications, and the factors beneath are far from being understood or predicted. The investigators hypothesize that some priming factors remain in the resection margin after surgery and act as a memory of the evolution of the disease, leading to the recurrence or complications. The following proposals are made:

1. defining and validating in humanized experimental models of intestinal inflammation the spatial and temporal dynamics of the postoperative complications-priming factors

2. integrating them into a machine-learning-driven model to determine risk indices of disease recurrence in IBD patients. This risk prediction model will not change the clinical decision-making process but will only be built for research. Consequently, patients enrolled in this study will be monitored and treated as per the standard of care.

This project will reveal possible causes and build methods predictive of postoperative complications ultimately resulting in changes in clinical management in the near future.

Detailed Description

A portion of patients with Inflammatory bowel disease often require surgical intervention since they do not respond to the current therapies. Besides this risk, patients may develop post-operative disease complications, and the factors beneath are far from being understood or predicted. The investigators hypothesize that some priming factors remain in the resection margin after surgery and act as a memory of the evolution of the disease, leading to the recurrence or complications. The following proposals are made:

1. defining and validating in humanized experimental models of intestinal inflammation the spatial and temporal dynamics of the postoperative complications-priming factors

2. integrating them into a machine-learning-driven model to determine risk indices of disease recurrence in IBD patients.

This risk prediction model will not change the clinical decision-making process but will only be built for research. Consequently, patients enrolled in this study will be monitored and treated as per standard of care. This project will reveal possible causes and build methods that could help predict postoperative complications ultimately resulting in changes in clinical management.

Study Timeline

• Study First Submitted: 2024-07-11
• Study First Submitted QC: 2024-07-18
• Study First Posted: 2024-07-23
• Study Start: 2025-02-27
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-14
• Primary Completion: 2025-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• adult (age >18 years) patients with histologically confirmed CD or UC undergoing intestinal resection due to stricturing disease, regardless of their current or past medical treatment;
• given that it is an observational study, also pregnant and breastfeeding patients could be included;
• able and willing to sign the informed consent.

Exclusion Criteria

• patients <18 years or > 70 years;
• patients with unconfirmed both UC and CD diagnoses;
• patients with superimposed dysplasia or cancer diagnosis and resections for which post- operative endoscopic assessment of recurrence is not feasible;
• patients unable or unwilling to sign the informed consent.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
UC patients	UC patients	patients with histologically confirmed UC undergoing intestinal resection due to stricturing disease. These patients will be divided into two groups: patients with postoperative recurrence and 5 without (control arm)
CD patients	CD patients	patients with histologically confirmed CD undergoing intestinal resection due to stricturing disease. Divided into two groups: patients with postoperative recurrence and 5 without (control arm)

Primary Outcome Measures

Name	Time	Method
To define spatial, cellular, and molecular characteristics of IBD-derived intestinal samples	6 months from surgery	To define the spatial transcriptome of UC and CD-derived intestinal mucosa, IBD-derived tissues will be analized by spatial transcriptomics, either at molecular or at microbiota level on formalin-fixed paraffin-embedded (FFPE) tissues stored at our pathology unit.

Secondary Outcome Measures

Name	Time	Method
To build the predictive model of postoperative complications based on spatially and temporally resolved IBD characteristics	6-12 months from surgery	Other variables to be considered are CD4+ T-cells from the processing of blood
To determine the mechanism underlying post-operative complications by exploiting in-vivo (mouse) experimental models of intestinal inflammation.	19-24 months from surgery	At the time of surgery, feces will be collected from patients. The microbial component from the IBD surgical specimens will be isolated and injected into humanized animal models.

Trial Locations

Locations (1)

IRCCS Ospedale San Raffaele; 🇮🇹 Milan, Italy