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NCT Number: NCT06516341

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.

Recruiting

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Key information

Age range

18 year–69 year

Sex eligibility

All sexes

Study type

Observational

Primary location

IRCCS Ospedale San Raffaele

Milan, Italy, 20132

Location status: Recruiting

Location contact

Alice Frontali, MD

SUB_INVESTIGATOR

Andrea Vignali, MD

SUB_INVESTIGATOR

Federica Ungaro, PhD

SUB_INVESTIGATOR

Federica Ungaro, PhD.

CONTACT

[email protected]

+39 0226437864

Luca Albarello, MD

SUB_INVESTIGATOR

Pierpaolo Sileri, MD, PhD.

CONTACT

[email protected]

+39 0226436275

Pierpaolo Sileri, MD, PhD.

PRINCIPAL_INVESTIGATOR

About this study

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:

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

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

Primary outcomes

  1. To define spatial, cellular, and molecular characteristics of IBD-derived intestinal samples

    Time frame: 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 outcomes

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

    Time frame: 6-12 months from surgery

    Other variables to be considered are CD4+ T-cells from the processing of blood

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

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Federica Ungaro, PhD.

CONTACT

[email protected]

+39 0226437864

Pierpaolo Sileri, MD. PhD.

CONTACT

[email protected]

+39 0226436275

Sponsors and collaborators

Lead sponsor

IRCCS Ospedale San Raffaele

Other

Collaborators

  • Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona
  • IRCCS Casa Sollievo della Sofferenza
  • Ministero della Salute, Italy

Registry information

Important dates

Study start
2025
Primary completion
2025
Study completion
2026
First posted
Jul 23, 2024
Registry last updated
Mar 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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