Study of the Sex Differences in Inflammatory Diseases in Children

NCT04815811 | Unknown

• 1 other identifier: P2019/LABO/SepsiX
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Sexual differences in innate immune response have been demonstrated and were mainly attributed to the influence of the sex steroids (1-18). However, recent clinical data revealed significant differences in inflammatory markers between boys and girls suffering from acute and chronic inflammatory diseases (19-23). Sex hormone levels in prepubertal children are particularly low and insufficient to explain the gender differences observed in inflammatory conditions from neonates to the elderly, suggesting the contribution of another mechanism, such as the influence of genes situated on the sex chromosomes and involved in the inflammatory response. The aim of this work is to evaluate the role of the X chromosome in the sex differences in inflammatory diseases in children. In order to discriminate more precisely the role of the X chromosome relatively to the sex steroids in the sex-specific inflammatory response, some innate immune functions related to X-linked genes will be evaluated in whole blood from prepubertal children of both sexes, suffering from acute inflammatory processes such as pyelonephritis caused by Escherichia coli, pneumonia with pleural effusion caused by Streptococcus pneumoniae or sepsis

Conditions

Sex Differences in Immune Response; Acute Inflammatory Diseases in Children

Keywords

Sex, immunology, inflammation, child, sepsis, UTI, pneumonia

Outcome Measures

Primary Outcomes (1)

• Whole blood production of cytokine IL-6

  The production of IL6 is measured by multiplex techniques.

  within 24 hours of hospital admission (Day 0)

Secondary Outcomes (38)

• Whole blood production of cytokine IL-1β

  within 24 hours of hospital admission (Day 0)

• Whole blood production of cytokine IL-8

  within 24 hours of hospital admission (Day 0)

• Whole blood production of cytokine IL-10

  within 24 hours of hospital admission (Day 0)

• Whole blood production of cytokine TNF-α

  within 24 hours of hospital admission (Day 0)

• Whole blood production of cytokine interferon-α

  within 24 hours of hospital admission (Day 0)

Study Arms (2)

Children suffering from acute inflammatory processes.

EXPERIMENTAL

The study population will consist of male and female children, aged from 6 months to 7 years old, admitted to the hospital for one of the three following types of acute inflammatory processes: * Urinary tract infection caused by Escherichia coli * Pneumonia with pleural effusion caused by Streptococcus pneumoniae * Sepsis

Other: Blood collection; Other: Stool collection

Control group

OTHER

Male and female children, aged from 6 months to 7 years old, admitted to the hospital for a scheduled operation for a non-inflammatory pathology.

Other: Blood collection

Interventions

Blood collection OTHER

Blood samples collections to evaluation of the potential role of the sex chromosomes in the innate immune response by analyzing inflammatory cytokine production (IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-α), studying the cell diapedesis receptor CD99 on PMNs, monocytes, and lymphocytes, analyzing the contribution of X-linked genes of the TLR pathways and the influence of X-linked miRNAs.

Children suffering from acute inflammatory processes.; Control group

Stool collection OTHER

Fecal sample collection to delineate microbiome contribution, we will study the gut microbiota in faecal samples obtained from the recruited patients.

Children suffering from acute inflammatory processes.

Eligibility Criteria

• Age: 6 Months - 7 Years
• Gender Eligibility Details: equity between male and female among the sample size
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male (XY) and female (XX) aged from 6 months to 7 years old.
• Subject hospitalized either for:
• (1) Urinary tract infection caused by Escherichia Coli, with:
• Temperature ≥ to 38,5°C
• Urinalysis
• Leukocyte esterase +
• AND/OR Nitrites +
• AND/OR pyuria (≥ 100WBC/mm³)
• AND/OR bacteriuria.
• Urinalysis
• Clean catch voided urine: \> 10\^4 Escherichia Coli colony form unit (CFU)/mm (urine collection method for children \>3 years old or toilet trained children or by stimulation for children \<3 years old)
• Transurethral bladder catheterisation: \> 10\^4 Escherichia Coli colony form unit (CFU)/mm³ (urine collection method for children \<3 years old).
• Suprapubic aspiration: \> 1 Escherichia Coli colony form unit (CFU)/mm³ (urine collection method for children \<3 years old).
• (2) Pneumonia with pleural effusion with :
• Temperature ≥ 38,5°C

You may not qualify if:

• Use of antithrombotic drugs (acetylsalicylic acid, thienopyridines, dipyridamol, glycoprotein IIb / IIIa antagonists, vitamin K antagonists, heparins).
• Congenital or acquired immunodeficiency: immunosuppressive drugs, hematopoietic stem cells transplantation, immunoglobulin therapy, extracorporeal membrane oxygenation (ECMO).
• Hemodialysis.
• h following cardiac operation of any type.
• Malignant cancer.
• HIV.

Sponsors & Collaborators

• Queen Fabiola Children's University Hospital: lead
• Belgium Kid's Fund: collaborator

Study Sites (1)

HUDERF

Brussels, 1020, Belgium

RECRUITING

Related Publications (35)

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MeSH Terms

Conditions

Coitus; Inflammation; Sepsis; Urinary Tract Infections; Pneumonia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Sexual Behavior; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Systemic Inflammatory Response Syndrome; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Alexandros Popotals, MD

  HUDERF

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexandros Popotas, MD

CONTACT

+32 2 477 24 24; alexandros.popotas@ulb.be

Nicolas Lefevre, MD, PhD

CONTACT

+32 2 477 23 41; nicolas.lefevre@huderf.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: March 25, 2021
• Study Start: August 17, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 25, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)