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

NCT06516341 | Recruiting

• 1 other identifier: PNRR-MCNT2-2023-12377779
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

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. 1.defining and validating in humanized experimental models of intestinal inflammation the spatial and temporal dynamics of the postoperative complications-priming factors
2. 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.

Conditions

Ulcerative Colitis; Crohn Disease

Keywords

Ulcerative Colitis; Crohn Disease; Stenosis; Post-operative recurrence; IBD; Biomarker prediction; Stricturing disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• To build the predictive model of postoperative complications based on spatially and temporally resolved IBD characteristics

  6-12 months from surgery

• To determine the mechanism underlying post-operative complications by exploiting in-vivo (mouse) experimental models of intestinal inflammation.

  19-24 months from surgery

Study Arms (2)

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

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

Interventions

CD patients PROCEDURE

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

UC patients PROCEDURE

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

UC patients

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, Italy, 20132, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

We will collect mucosal brushes (as per clinical practice) and additional volume of blood (during blood collection as per clinical practice) and feces at the time of surgery ad hoc for the study

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease; Constriction, Pathologic

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Pierpaolo Sileri, MD. PhD.

CONTACT

+39 0226436275; sileri.pierpaolo@hsr.it

Federica Ungaro, PhD.

CONTACT

+39 0226437864; ungaro.federica@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 23, 2024
• Study Start: February 27, 2025
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)