Pediatric Immune Response to Multi-Organ Dysfunction

Multiple Organ Dysfunction Syndrome Clinical Trial

— PedIMOD  

Official title:

Pediatric Immune Response to Multi-Organ Dysfunction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04438460
• Other study ID #: 69HCL20_0068
• Secondary ID: 2020-A00343-36
• Status: Completed
• Phase: N/A
• Start date: July 29, 2020
• Est. completion date: April 16, 2024

Study information

• Verified date: May 2024
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: April 16, 2024
• Est. primary completion date: April 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 12 Years

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Organ Dysfunction Syndrome
• Multiple Organ Failure

Intervention

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.

Locations

Country	Name	City	State
France	Hôpital Femme Mère Enfant	Bron
France	Hopital Mère Enfant	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Myeloid Derived Suppressor Cells (MDSC) measurement	Characterization of MDSC will be measured and compared between patient and control	Day 1
Secondary	Intra-cellular production of tumor necrosis factor alpha (TNFa) by the monocyte	Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF a by the monocyte. It will be compared between patient and control.	Day 1
Secondary	MDSC measurement	Characterization of MDSC will be measured	Day 3
Secondary	Intra-cellular production of TNFa by the monocyte	Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF a by the monocyte.	Day 3
Secondary	Monocytic and dendritic subpopulations measurement	Characterization of monocytic and dendritic subpopulations will be realized and compared between patient and control.	Day 1
Secondary	Gamma-delta T lymphocytes measurement	Characterization of gamma-delta T lymphocytes will be realized and compared between patient and control.	Day 1
Secondary	Monocytic and dendritic subpopulations measurement	Characterization of monocytic and dendritic subpopulations will be realized	Day 3
Secondary	Gamma-delta T lymphocytes measurement	Characterization of gamma-delta T lymphocytes will be realized	Day 3
Secondary	Monocytic and dendritic subpopulations measurement	Characterization of monocytic and dendritic subpopulations will be realized	Day 60
Secondary	Gamma-delta T lymphocytes measurement	Characterization of gamma-delta T lymphocytes will be realized	Day 60