Role of Altered Intestinal Permeability and Lipopolysaccharide in Thrombotic Risk and Vascular Injury in IBD Patients (PERVASC-IBD)

Role of Altered Intestinal Permeability and Lipopolysaccharide in Thrombotic Risk and Vascular Injury of Patients With Chronic Inflammatory Bowel Disease

Chronic inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic immune-mediated inflammation primarily affecting the gastrointestinal tract. Venous and arterial thromboembolic events are significant extra-intestinal manifestations of IBD, but their pathogenic mechanisms are not fully understood. IBD patients have double the risk of venous thromboembolism (VTE) compared to the general population, with particularly high risk in pediatric patients, and an increased mortality rate. They also face a higher risk of early atherosclerosis and future cardiovascular events, such as myocardial infarction, ischemic stroke, and peripheral artery disease. The prevalence of thromboembolic events in IBD ranges from 1.3% to 7.7%, with venous events at around 5% and ischemic heart disease, cerebrovascular disease, and peripheral artery disease at 1-2%.

Study Overview

• Status: Not yet recruiting
• Conditions: IBD
• Intervention / Treatment: Procedure: examinations

Detailed Description

Chronic inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic immune-mediated inflammation primarily affecting the gastrointestinal tract. Venous and arterial thromboembolic events are significant extra-intestinal manifestations of IBD, but their pathogenic mechanisms are not fully understood. IBD patients have double the risk of venous thromboembolism (VTE) compared to the general population, with particularly high risk in pediatric patients, and an increased mortality rate. They also face a higher risk of early atherosclerosis and future cardiovascular events, such as myocardial infarction, ischemic stroke, and peripheral artery disease. The prevalence of thromboembolic events in IBD ranges from 1.3% to 7.7%, with venous events at around 5% and ischemic heart disease, cerebrovascular disease, and peripheral artery disease at 1-2%.Several mechanisms contribute to the increased thrombotic risk in IBD, including platelet abnormalities (thrombocytosis and altered platelet function), coagulation factor alterations (e.g., fibrinogen, thrombin), and fibrinolysis defects. Increased oxidative stress and endothelial damage, especially during active disease phases, also play a role. The oxidative stress, caused by reactive oxygen and nitrogen species produced in IBD, leads to molecular and cellular damage, impaired cell homeostasis, and increased mucosal barrier permeability.These changes alone do not fully explain the heightened thrombotic risk in IBD. A reduction in intestinal microbiota diversity and the altered production of metabolites like Trimethylamine-N-oxide (TMAO) may also contribute, along with intestinal permeability changes that allow bacterial products, including lipopolysaccharide (LPS), to enter the bloodstream. LPS, a component of the outer membrane of Gram-negative bacteria, can stimulate low-grade endotoxemia, promoting atherosclerosis and increasing thrombotic risk. Although direct data on this are lacking, these pathological alterations suggest that increased intestinal permeability and circulating LPS may contribute to the elevated venous and arterial thrombotic risk in IBD patients.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of IBD (both CD and UC, both in active and quiescent stages of disease)
• Age > 18 years
• Signature of informed consent

Exclusion Criteria:

• Other inflammatory states other than IBD (e.g., neoplasm, autoimmune diseases, liver cirrhosis)
• Age < 18 years
• Pregnant woman
• Lack of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Experimental	Procedure: examinations; Echo-Doppler and blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring altered intestinal permeability and increased thrombotic risk	altered intestinal permeability will be assessed by measurement of serum LPS and thrombotic risk by echo-Doppler examination	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring the relationship between intestinal permeability and how these factors contribute to inflammation and gut microbiota changes in health and disease.	Alteration of intestinal permeability will be assessed by microbiota analysis	1 year

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2025
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): June 15, 2036

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Vascular System Injuries
• Other Study ID Numbers: 7035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No