Clinical trial NCT06516341: Spatially and Temporally Resolving Predictive Biomarkers of Postoperative Recurrence and Complications in Chronic Intestinal Inflammation
Official title: Spatially and Temporally Resolving Predictive Biomarkers of Postoperative Recurrence and Complications in Chronic Intestinal Inflammation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ulcerative Colitis
Crohn Disease
Keywords: Ulcerative Colitis
Crohn Disease
Stenosis
Post-operative recurrence
IBD
Biomarker prediction
Stricturing disease
Lead sponsor: IRCCS Ospedale San Raffaele
Sponsor class: OTHER
Collaborators: name: IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo
name: Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona
name: Ministero della Salute, Italy
First posted: 2024-07-23
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To define spatial, cellular, and molecular characteristics of IBD-derived intestinal samples
timeFrame: 6 months from surgery
Secondary outcomes:
measure: To build the predictive model of postoperative complications based on spatially and temporally resolved IBD characteristics
timeFrame: 6-12 months from surgery
measure: To determine the mechanism underlying post-operative complications by exploiting in-vivo (mouse) experimental models of intestinal inflammation.
timeFrame: 19-24 months from surgery
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
References: