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

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.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease; Ulcerative Colitis
• Intervention / Treatment: Procedure: UC patients; Procedure: CD patients

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 Type: Observational
• Enrollment (Estimated): 35

Contacts and Locations

• Study Contact: Name: Federica Ungaro, PhD.; Phone Number: +39 0226437864; Email: ungaro.federica@hsr.it
• Study Contact Backup: Name: Pierpaolo Sileri, MD. PhD.; Phone Number: +39 0226436275; Email: sileri.pierpaolo@hsr.it

Study Locations

• Italy
  • Milan, Italy, 20132
    • Recruiting
    • IRCCS Ospedale San Raffaele
    • Contact: Federica Ungaro, PhD.; Phone Number: +39 0226437864; Email: ungaro.federica@hsr.it
    • Contact: Federica Ungaro, PhD
    • Contact: Luca Albarello, MD
    • Contact: Pierpaolo Sileri, MD, PhD.; Phone Number: +39 0226436275; Email: sileri.pierpaolo@hsr.it
    • Contact: Pierpaolo Sileri, MD, PhD.
    • Contact: Andrea Vignali, MD
    • Contact: Alice Frontali, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is an observational multicenter study with additional procedures performed on patients with an established diagnosis of UC and CD. It consists of a prospective and a retrospective part. The prospective part involves surgical leftover and blood collected at the time of surgery ad hoc for the study, without other risks for the patients. For the retrospective analysis, paraffin-embedded specimens already stored in the pathology unit from at least two years before the project starting date (from 1st August 2022 to 31st August 2024), will be used. Moreover, we will select and include in this study adult (age ≥18 years) patients with histologically confirmed CD or UC who have undergone surgery as per standard of care and whose surgical tissue- and blood-derived cell-suspensions have been previously collected for the already approved project IBD Biobank and stored at -80° C. The retrospective analysis will include IBD biobank samples collected since 1st August 2022 up to August 2024.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
UC patients; Patients with histologically confirmed UC undergoing intestinal resection due to stricturing disease. These patients will be divided into two groups: patients with (case group) and without (control group) postoperative recurrence	Procedure: UC patients; The study will involve the collection of leftover surgical material after pathologist analysis, mucosal brushes, an additional volume of blood and feces of patients at the time of surgery
CD patients; Patients with histologically confirmed CD undergoing intestinal resection due to stricturing disease. Divided into two groups: patients with (case group) and without (control group) postoperative recurrence	Procedure: CD patients; The study will involve the collection of leftover surgical material after pathologist analysis, mucosal brushes, an additional volume of blood and feces of patients at the time of surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define spatial, cellular, and molecular characteristics of IBD-derived intestinal samples	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.	6 months from surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To build the predictive model of postoperative complications based on spatially and temporally resolved IBD characteristics	Other variables to be considered are CD4+ T-cells from the processing of blood	6-12 months from surgery
To determine the mechanism underlying post-operative complications by exploiting in-vivo (mouse) experimental models of intestinal inflammation.	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.	19-24 months from surgery

Collaborators and Investigators

• Sponsor: IRCCS Ospedale San Raffaele
• Collaborators: Ministero della Salute, Italy; Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona; IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2025
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; IBD; Stenosis; Crohn Disease; Post-operative recurrence; Biomarker prediction; Stricturing disease
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Recurrence; Colitis; Colitis, Ulcerative; Inflammation; Crohn Disease
• Other Study ID Numbers: PNRR-MCNT2-2023-12377779

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No