Comparison Diagnostic Tests for the Diagnosis of CYTOmegalovirus Organ Disease in Patients With intestinalBOweL Diseases

Recruiting

• Conditions: Cytomegalovirus (CMV); Inflammatory Bowel Disease (IBD)

• Registration Number: NCT06793124
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Brief Summary

Observational, single-center, non-pharmacological, prospective study of adult patients affected by Inflammatory Bowel Disease (IBD) with an ongoing disease exacerbation requiring hospitalization

Detailed Description

Patients with chronic inflammatory bowel disease (IBD) are subject to an increased risk of infectious events. This is secondary in part to an intrinsic dysregulation of the immune system, in part to the increasingly frequent need to subject the patient to immunomodulatory therapies for the management of the underlying disease. In this context, it is very difficult from a clinical point of view to be able to demonstrate a concomitant intestinal cytomegalovirus (CMV) organ disease, since the symptoms are often nonspecific or overlapping. Following the guidelines, since there is no well-defined cut-off for viral replication in blood, the gold standard for the diagnosis of intestinal CMV disease remains organ-specific biopsy with immunohistochemical research of the included nuclei. However, at the moment there are no reliable findings for this method that can distinguish a clinically insignificant reactivation from a true organ disease. However, plasma CMV viremia measurement is generally recommended in this setting since active replication in blood could be an epiphenomenon of organ disease. Similarly, some studies have shown a correlation between CMV gastroenteritis and detection of CMV-DNA in fecal samples. Furthermore, several methods have been developed in recent years, and their diagnostic yield has not yet been fully defined. The evaluation of viral load on tissue biopsy by PCR is a method that is gaining ground, and currently the guidelines suggest it in association with immunohistochemistry itself. Some authors suggest a cut-off of 250 cp/mg of tissue to define organ disease. In this setting, the initiation of a specific antiviral treatment remains non-standardized, and it presents expected side effects, primarily bone marrow suppression. However, in several studies, an increased need for surgery for uncontrolled underlying disease has been found in patients with CMV organ disease who are not treated promptly.

From a clinical point of view, in patients who have worsening symptoms related to IBD, being able to identify early markers able to predict CMV colonic organ disease is of crucial importance, since early specific treatment could increase the chances of a favorable outcome, sparing the patient the need for abdominal surgery. In this context, plasma and fecal CMV-DNA dosage represents a rapid diagnostic method, with a turn-over of about 24 hours, which could be an epiphenomenon of the colonic disease itself.

The primary objective of the study is to evaluate the diagnostic performance of different methods used for the diagnosis of CMV infection, namely CMV-DNA on blood and CMV-DNA on fecal samples - comparing them with the gold standard, namely immunohistochemical investigation on biopsy sample in patients affected by IBD with clinical worsening requiring hospitalization.

Study Timeline

• Study Start: 2024-04-02
• Status Verified: 2024-12
• Study First Submitted: 2024-12-01
• Study First Submitted QC: 2025-01-20
• Last Update Submitted: 2025-01-20
• Study First Posted: 2025-01-27
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-09-30
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Patients aged ≥18 years with Inflammatory Bowel Disease (IBD) with worsening of IBD-related symptoms requiring hospital admission
• Signing of informed consent
• Performed endoscopic biopsies to confirm/exclude CMV organ disease

Exclusion Criteria

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Evaluation of the diagnostic performance of methods for CMV infection diagnosis	Each samples taken from the patients will be tested through study completion (average of 2 year)	Evaluation of the diagnostic performance of different methods used for the diagnosis of CMV infection, i.e. CMV-DNA on blood and CMV-DNA on fecal samples - comparing them with the gold standard, i.e. immunohistochemical investigation on biopsy sample in patients affected by IBD with clinical worsening requiring hospitalization

Secondary Outcome Measures

Name	Time	Method
Immunohistochemistry on biopsy sample and PCR for CMV	Each samples taken from the patients will be tested through study completion (average of 2 year)	Verify the concordance between positive/borderline immunohistochemistry (microscopic examination using specific antibodies to detect the presence of CMV) on biopsy sample and PCR (Polymerase Chain Reaction) for CMV on the sample itself
Immunohistochemical pattern severity and clinical evolution	Each samples taken from the patients will be tested through study completion (average of 2 year)	Verify if there is a relationship between the severity of the immunohistochemical pattern and clinical evolution and/or the need for major abdominal surgery (colectomy, stoma placement, etc.). Measurement Tools: Immunohistochemistry (Analysis of the severity of the immunohistochemical pattern in biopsy samples, focusing on CMV-related markers); Clinical Assessment (Evaluation of clinical evolution, including the need for major abdominal surgeries)
Evaluation of viral load in biopsy samples	Each samples taken from the patients will be tested through study completion (average of 2 year)	Verify whether there is a relationship between viral load on biopsy sample and clinical evolution and/or need for major abdominal surgery (colectomy, stoma placement, etc.); Correlation between viral load in biopsy samples and clinical outcomes and/or implications for major abdominal surgery (colectomy, stoma placement, etc.)
Evaluation of the Impact of Antiviral Treatment	Each samples taken from the patients will be tested through study completion (average of 2 year)	Evaluate the impact of an antiviral treatment on clinical evolution and/or need for major abdominal surgery (colectomy, stoma placement, etc.)
Evaluation of clinical evolution of patients with and without CMV organ disease at 30 days	At the follow-up at 30 days (through study completion, an average of 2 year)	Compare the clinical evolution at 30 days of patients with and without CMV organ disease. The clinical evolution of the patient is understood as the clinical response/refractoriness to medical treatments and the potential need for unplanned major abdominal rescue surgery at the end of the follow-up (+30 days). The clinical response will be evaluated based on the normalization of bowel function (normalization of daily evacuation frequency) and the disappearance of systemic symptoms such as fever, if present, at the end of the follow-up (+30 days).

Trial Locations

Locations (1)

IRCCS Azienda Ospedaliero-Universitaria di Bologna; 🇮🇹 Bologna, Italy