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Completed

NCT Number: NCT04438460

Pediatric Immune Response to Multi-Organ Dysfunction

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.

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Key information

Conditions

Multiple Organ Dysfunction Syndrome Coinfection Infections Multiple Organ Failure Pathologic Processes Pathological Conditions, Signs and Symptoms Shock

Age range

1 month–12 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hôpital Femme Mère Enfant, Bron, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

blood test

Biological

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.

Primary outcomes

  1. Secondary acquired infection (SAI)

    Time frame: Day 60

    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.

Secondary outcomes

  1. blood counts : Characterization of alterations in the myeloid lineage

    Time frame: Day 1

    Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.

  2. mHLA-DR expression : Characterization of alterations in the myeloid lineage

    Time frame: Day 1

    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

  3. transcriptome : Characterization of alterations in the myeloid lineage

    Time frame: Day 1

    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.

  4. plasma cytokines : Characterization of alterations in the myeloid lineage

    Time frame: Day 1

    Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.

  5. blood counts : Characterization of alterations in the myeloid lineage

    Time frame: Day 3

    Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months

  6. mHLA-DR expression : Characterization of alterations in the myeloid lineage

    Time frame: Day 3

    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.

  7. transcriptome : Characterization of alterations in the myeloid lineage

    Time frame: Day 3

    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.

  8. plasma cytokines : Characterization of alterations in the myeloid lineage

    Time frame: Day 3

    Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.

  9. blood counts : Characterization of alterations in the myeloid lineage

    Time frame: Day 60

    Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.

  10. mHLA-DR expression : Characterization of alterations in the myeloid lineage

    Time frame: Day 60

    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.

  11. transcriptome : Characterization of alterations in the myeloid lineage

    Time frame: Day 60

    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.

  12. plasma cytokines : Characterization of alterations in the myeloid lineage

    Time frame: Day 60

    Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.

  13. mHLA-DR measurement

    Time frame: Day 60

    Evaluation of the immunological recovery at month 2 with regard to the initial state and in comparison with the controls.

  14. Myeloid Derived Suppressor Cells (MDSC) measurement

    Time frame: Day 1

    Characterization of MDSC will be measured and compared between patient and control

  15. Intra-cellular production of tumor necrosis factor alpha (TNFα) by the monocyte

    Time frame: Day 1

    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.

  16. MDSC measurement

    Time frame: Day 3

    Characterization of MDSC will be measured

  17. Intra-cellular production of TNFα by the monocyte

    Time frame: Day 3

    Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte.

  18. Monocytic and dendritic subpopulations measurement

    Time frame: Day 1

    Characterization of monocytic and dendritic subpopulations will be realized and compared between patient and control.

  19. Gamma-delta T lymphocytes measurement

    Time frame: Day 1

    Characterization of gamma-delta T lymphocytes will be realized and compared between patient and control.

  20. Monocytic and dendritic subpopulations measurement

    Time frame: Day 3

    Characterization of monocytic and dendritic subpopulations will be realized

  21. Gamma-delta T lymphocytes measurement

    Time frame: Day 3

    Characterization of gamma-delta T lymphocytes will be realized

  22. Monocytic and dendritic subpopulations measurement

    Time frame: Day 60

    Characterization of monocytic and dendritic subpopulations will be realized

  23. Gamma-delta T lymphocytes measurement

    Time frame: Day 60

    Characterization of gamma-delta T lymphocytes will be realized

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Acronym: PedIMOD

Important dates

Study start
2020
Primary completion
2024
Study completion
2024
First posted
Jun 18, 2020
Registry last updated
May 29, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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