Comparison Diagnostic Tests for the Diagnosis of CYTOmegalovirus Organ Disease in Patients With intestinalBOweL Diseases (CYTO-BOLD)

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

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

Study Overview

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

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 Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Matteo Rinaldi, MD; Phone Number: +390512144302; Email: matteo.rinaldi23@unibo.it

Study Locations

• Italy
  • Bologna
    • Bologna, Bologna, Italy, 40138
      • Recruiting
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna
      • Contact: Matteo Rinaldi, MD; Phone Number: +390512144302; Email: matteo.rinaldi23@aosp.bo.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with inflammatory bowel disease (IBD), either outpatients or requiring hospital admission, who undergo colonic biopsy for recurrence of the underlying disease, will be screened for inclusion

Description

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: /

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Adult patients with inflammatory bowel disease (IBD); Adult patients with inflammatory bowel disease (IBD) who undergo colonic biopsy for recurrence of the underlying disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Performance of CMV-DNA Quantification in Blood and Fecal Samples Compared to Immunohistochemistry on Biopsy for CMV Infection Diagnosis	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	Each samples taken from the patients will be tested through study completion (average of 2 year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance Between Positive/Borderline Immunohistochemistry and PCR for CMV on Biopsy Samples	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	Each samples taken from the patients will be tested through study completion (average of 2 year)
Severity of Immunohistochemical Pattern and Its Relationship with Clinical Evolution	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)	Each samples taken from the patients will be tested through study completion (average of 2 year)
Viral Load in Biopsy Samples and Its Correlation with Clinical Outcomes	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.)	Each samples taken from the patients will be tested through study completion (average of 2 year)
Impact of Antiviral Treatment on Clinical Evolution	Evaluate the impact of an antiviral treatment on clinical evolution and/or need for major abdominal surgery (colectomy, stoma placement, etc.)	Each samples taken from the patients will be tested through study completion (average of 2 year)
Clinical Evolution at 30 Days in Patients With and Without CMV Organ Disease	Evaluate the clinical evolution of patients with and without Cytomegalovirus (CMV) organ disease at 30 days. Clinical response will be defined by the normalization of bowel function (i.e., normalization of daily evacuation frequency) and the disappearance of systemic symptoms, such as fever, if present. Clinical refractoriness will be assessed based on the failure to achieve these clinical improvements and the potential need for unplanned major abdominal rescue surgery by the end of the follow-up period (+30 days). The comparison will include: Clinical Response: Improvement in bowel function and resolution of systemic symptoms. Clinical Refractoriness: Lack of improvement and requirement for unplanned major abdominal surgery.	At the follow-up at 30 days (through study completion, an average of 2 year)

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Matteo Rinaldi, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 1, 2024
• First Submitted That Met QC Criteria: January 20, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: PCR; Inflammatory Bowel Disease (IBD); Cytomegalovirus (CMV); Tissue biopsy
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases
• Other Study ID Numbers: CYTO-BOLD

Drug and device information, study documents

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