Neutrophil Oxidative Burst in Early and Late Onset Pediatric Inflammatory Bowel Disease

ABSTRACT Introduction Residual or absent oxidase function in peripheral neutrophils may point to an inborn defect of neutrophil function - chronic granulomatous disease (CGD) - whereas low to normal oxidative burst capacity has been linked to variants in various members of the NADPH-complex.

Aims To assess the clinical value of routinely measuring oxidative burst activity of granulocytes in pediatric patients diagnosed with very early onset IBD (VEO-IBD) and late onset IBD.

Objectives To investigate possible correlations between neutrophil function and IBD disease activity and to inquire the presence of genetic variants in those with low to absent oxidative burst. To identify the rate of monogenic VEO-IBD in our cohort.

Materials and Methods The proposal constitutes a collaborative effort among Romanian pediatric tertiary care centers to examine the value of assessing neutrophil function in all pediatric IBD patients. Children aged <18 years diagnosed with Crohn's disease, ulcerative colitis or IBD-undetermined and age-matched healthy controls are recruited. A DHR flow cytometry assay is performed in included subjects and controls. Reduced or absent burst activity will lead to genetic testing in search of overt immunodeficiency or susceptibility variants. All VEO-IBD patients will have an immunological work-up in search of a primary immunodeficiency.

Expected Results We anticipate to include a number of 150 pediatric patients with IBD over 12 months from the three pediatric gastroenterology units in Bucharest, Romania. We expect to identify an overall diminished neutrophil function in IBD patients versus controls and possible variants in the NADPH-complex genes.

Study Overview

• Status: Recruiting
• Conditions: Chronic Granulomatous Disease
• Intervention / Treatment: Diagnostic test: Phagoburst; Diagnostic test: Lymphocytes subsets; Diagnostic test: Genetic testing

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Alexis Virgil Cochino, MD, PhD; Phone Number: +40723193648; Email: alexis_virgil@yahoo.com

Study Locations

• Romania
  • County
    • Bucharest, County, Romania, 041249
      • Recruiting
      • National Institute for Mother and Child Health Alessandrescu Rusescu
      • Contact: I
      • Contact: Alexis Virgil Cochino, MD, PhD; Phone Number: +40723196648; Email: alexis_virgil@yahoo.com
      • Principal Investigator: Alexis Virgil Cochino, MD, PhD
      • Sub-Investigator: Andreea Ioan, MD
      • Sub-Investigator: Felicia Galos, MD, PhD
      • Sub-Investigator: Iulia Tincu, MD, PhD
      • Sub-Investigator: Cristina Becheanu, MD, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population will include pediatric patients diagnosed with IBD (right from the diagnosis or anytime during the disease course) from three different gastroenterology units in Bucharest, Romania.

Screening tests for an imunological disease (neutrophil oxidative burst, lymphocyte subsets) will be performed in included patients and healthy controls by the home institution.

Description

Inclusion Criteria:

Subjects:

1. age under 18 years;
2. confirmed diagnosis of IBD fulfilling standard diagnosis criteria (clinical, radiological, endoscopical, histological features)
3. parental/guardian consent for study enrollment

Controls:

Healthy age-gender matched controls

Exclusion Criteria:

1. IBD associated to an already defined monogenic defect
2. Diagnosis of IBD uncertain
3. HIV/TB positive

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Inflammatory bowel disease patients; Pediatric patients (under 18 years of age) diagnosed with IBD	Diagnostic test: Phagoburst; The main objective is to perform oxidative burst activity in pediatric patients with a definitive diagnosis of IBD and compare them with healthy controls.; Diagnostic test: Lymphocytes subsets; To determine lymphocytes subsets in patients with suspicion of IEI; Diagnostic test: Genetic testing; Perform targeted genetic testing in those with reduced to absent oxidative activity in search of PIDs and susceptibility variants
Healthy controls; Healthy chidren (no chronic disease)	Diagnostic test: Phagoburst; The main objective is to perform oxidative burst activity in pediatric patients with a definitive diagnosis of IBD and compare them with healthy controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxidative burst activity in IBD patients	Perform oxidative burst activity in pediatric patients with a definitive diagnosis of IBD and compare them with healthy controls.	12 months
Genetic testing in patients with suspicion of IEI	Perform targeted genetic testing in those with reduced to absent oxidative activity in search of PIDs and susceptibility variants	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Role of burst activity in disease phenotype	Find correlations between burst activity and disease activity	12 months

Collaborators and Investigators

• Sponsor: National Institute for Mother and Child Health Alessandrescu Rusescu
• Collaborators: Marie Curie Emergency Children's Hospital, Bucharest; Victor Gomoiu Children's Hospital, Bucharest

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: inflammatory bowel disease; chronic granulomatous disease; inborn errors of immunity
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Hematologic Diseases; Gastrointestinal Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Gastroenteritis; Leukocyte Disorders; Phagocyte Bactericidal Dysfunction; Chronic Disease; Inflammatory Bowel Diseases; Intestinal Diseases; Granulomatous Disease, Chronic
• Other Study ID Numbers: IBD20232024

Drug and device information, study documents

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