Pediatric Immune Response to Multi-Organ Dysfunction (PedIMOD)

Multiple organ dysfunction (MOD) is defined by the association of at least two failures of vital organs, with various etiologies (septic shock, polytrauma, acute respiratory distress syndrome, etc.). Associated mortality remains high in children (between 20 and 50%).

In septic shock, one of the main causes of MOD, induced immunosuppression can occur, with immune alterations affecting all cells of immunity. This induced immunosuppression is associated with an additional risk of secondary acquired infections and death in adults. Among all the cells and all the markers studied, the expression of Human Leukocyte Antigen - DR isotype (HLA-DR) on the surface of the monocyte (mHLA-DR, expressed in number of sites per cell) appeared as one of the best biomarkers of this induced immunosuppression. Decreased expression of monocyte Human Leukocyte Antigen - DR isotype (mHLA-DR) in adults is linked to an increased risk of developing secondary infection and death.

These results were confirmed by team in the context of pediatric septic shock, with an attack of innate immunity in the foreground. Persistent lowering of mHLA-DR for more than 3 days after onset of shock was associated with the occurrence of secondary acquired infections: 50% of children had mHLA-DR of less than 8000 sites / cells on D3, of which 60 % developed secondary infection within 30 days. No child with mHLA-DR greater than 8000 sites / cells had secondary infection.

Such immune alterations appear to be non-specific for septic shock, as they have also been described after multiple trauma or severe respiratory infections.

The hypothesize is that multi-systemic aggression leading to multi-visceral failure syndrome could also lead to significant immunosuppression, regardless of the etiology of this MOD.

At present, the proportion of persistent immunosuppression induced by MOD, all etiologies combined, is poorly documented in pediatrics. Estimating this proportion in a large pediatric cohort, while exploring as fully as possible the associated immune alterations and acquired secondary infections, would improve the pathophysiological understanding and pediatric specificities of this phenomenon.

Study Overview

• Status: Recruiting
• Conditions: Multiple Organ Dysfunction Syndrome
• Intervention / Treatment: Biological: Blood test

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Solenn REMY, MD, PhD; Phone Number: +33 0472 129 746; Email: solene.remy@chu-lyon.fr
• Study Contact Backup: Name: Tiphanie Ginhoux; Phone Number: +33 0427 857 723; Email: tiphanie.ginhoux01@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69500
    • Recruiting
    • Hôpital Femme Mère Enfant
    • Contact: Solenn REMY, MD,PhD; Phone Number: +33 0472 129 746; Email: solene.remy@chu-lyon.fr
    • Contact: Tiphanie Ginhoux; Phone Number: +33 0427 857 723; Email: tiphanie.ginhoux@chu-lyon.fr
    • Principal Investigator: Solenn REMY, MD,PhD
    • Sub-Investigator: Etienne JAVOUHEY, PU, PH
    • Sub-Investigator: Dominique CHASSARD, PU, PH
  • Nantes, France, 44093
    • Not yet recruiting
    • Hopital Mère Enfant
    • Contact: Alexis Chenouard, MD, PhD; Phone Number: +33 02.40.08.34.83; Email: Alexis.CHENOUARD@chu-nantes.fr
    • Principal Investigator: Alexis Chenouard, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patient Group:

• 1 month < Age < 12 years
• Multiple organ dysfunction within 48 hours following intensive care unit admission
• Beneficiary of a social security scheme.
• Consent signed by at least one parent / holder of parental authority

Control Group:

• 1 month < Age < 12 years
• Hospitalized for simple elective surgery
• Beneficiary of a social security scheme.
• Consent signed by at least one parent / holder of parental authority

Exclusion Criteria:

Patient Group:

• Weight < 5 kg
• Known immunosuppression
• Prolonged corticotherapy
• Chronic inflammatory disease
• Malignant pathology with ongoing treatment
• Hepatic cirrhosis
• Polymerase Chain Reaction (PCR) Severe acute respiratory syndrome coronavirus (SARS-CoV-2) positive or patient with Pediatric Inflammatory Multisystem Syndrome (PIMS)
• Pediatric inflammatory multisystem syndrome (PIMS)

Control Group:

• Weight < 5 kg
• Known immunosuppression
• Prolonged corticotherapy
• Chronic inflammatory disease
• Malignant pathology with ongoing treatment
• Ongoing infection
• Organ failure
• Hepatic cirrhosis
• PCR SARS-CoV-2 positive or patient with Pediatric Inflammatory Multisystem Syndrome (PIMS)
• Pediatric inflammatory multisystem syndrome (PIMS)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient group; 150 children aged 1 month to 12 years with multi-visceral failure syndrome within 48 hours of hospitalization in pediatric resuscitation will be included in this study	Biological: Blood test; For patient group, blood tests will be performed at day 1-2, day 3-5 and day 60. For control group, blood test will be performed the day of elective surgery.
Other: Control group; 60 children aged 1 month to 12 years hospitalized for simple elective surgery will be included in this study	Biological: Blood test; For patient group, blood tests will be performed at day 1-2, day 3-5 and day 60. For control group, blood test will be performed the day of elective surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary acquired infection (SAI)	This criterion will be related to the duration of follow-up and expressed as an incidence of SAI occurrence.This incidence will be calculated in the two groups "Presence of immunosuppression" and "Absence of immunosuppression", defined from the value of mHLA-DR at D3-D5: "Presence of immunosuppression" if mHLA-DR < 8000 sites/cells and "Absence of immunosuppression" if mHLA-DR ≥ 8000 sites/cells. The diagnosis of secondary acquired infection will be made by an independent committee.	Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood counts : Characterization of alterations in the myeloid lineage	Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 1
mHLA-DR expression : Characterization of alterations in the myeloid lineage	mHLA-DR expressed as a number of site / cell will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months	Day 1
transcriptome : Characterization of alterations in the myeloid lineage	Gene expression through messenger ribonucleic acid (mRNA) analysis will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 1
plasma cytokines : Characterization of alterations in the myeloid lineage	Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 1
blood counts : Characterization of alterations in the myeloid lineage	Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months	Day 3
mHLA-DR expression : Characterization of alterations in the myeloid lineage	mHLA-DR expressed as a number of site / cell will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 3
transcriptome : Characterization of alterations in the myeloid lineage	Gene expression through messenger ribonucleic acid (mRNA) analysis will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 3
plasma cytokines : Characterization of alterations in the myeloid lineage	Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 3
blood counts : Characterization of alterations in the myeloid lineage	Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 60
mHLA-DR expression : Characterization of alterations in the myeloid lineage	mHLA-DR expressed as a number of site / cell will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 60
transcriptome : Characterization of alterations in the myeloid lineage	Gene expression through messenger ribonucleic acid (mRNA) analysis will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 60
plasma cytokines : Characterization of alterations in the myeloid lineage	Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.	Day 60
mHLA-DR measurement	Evaluation of the immunological recovery at month 2 with regard to the initial state and in comparison with the controls.	Day 60
Myeloid Derived Suppressor Cells (MDSC) measurement	Characterization of MDSC will be measured and compared between patient and control	Day 1
Intra-cellular production of tumor necrosis factor alpha (TNFα) by the monocyte	Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte. It will be compared between patient and control.	Day 1
MDSC measurement	Characterization of MDSC will be measured	Day 3
Intra-cellular production of TNFα by the monocyte	Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte.	Day 3
Monocytic and dendritic subpopulations measurement	Characterization of monocytic and dendritic subpopulations will be realized and compared between patient and control.	Day 1
Gamma-delta T lymphocytes measurement	Characterization of gamma-delta T lymphocytes will be realized and compared between patient and control.	Day 1
Monocytic and dendritic subpopulations measurement	Characterization of monocytic and dendritic subpopulations will be realized	Day 3
Gamma-delta T lymphocytes measurement	Characterization of gamma-delta T lymphocytes will be realized	Day 3
Monocytic and dendritic subpopulations measurement	Characterization of monocytic and dendritic subpopulations will be realized	Day 60
Gamma-delta T lymphocytes measurement	Characterization of gamma-delta T lymphocytes will be realized	Day 60

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Estimated): September 29, 2024
• Study Completion (Estimated): September 29, 2024

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Immunosuppression; Pediatrics; Multiple organ dysfunction; mHLA-DR; Secondary infection
• Additional Relevant MeSH Terms: Pathologic Processes; Shock; Multiple Organ Failure
• Other Study ID Numbers: 69HCL20_0068; 2020-A00343-36 (Other Identifier: ID-RCB)

Drug and device information, study documents

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