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Pediatric Immune Response to Multi-Organ Dysfunction (PedIMOD)

Primary Purpose

Multiple Organ Dysfunction Syndrome

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Blood test
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Multiple Organ Dysfunction Syndrome focused on measuring Multiple organ dysfunction, Immunosuppression, mHLA-DR, Pediatrics, Secondary infection

Eligibility Criteria

1 Month - 12 Years (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Hôpital Femme Mère EnfantRecruiting
  • Hopital Mère Enfant

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Patient group

Control group

Arm Description

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

60 children aged 1 month to 12 years hospitalized for simple elective surgery will be included in this study

Outcomes

Primary Outcome Measures

mHLA-DR measurement
The proportion of children with mHLA-DR < 8000 sites / cells on Day 3 - Day 5 will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months. The diagnosis of secondary acquired infection will be made by an independent committee.

Secondary Outcome Measures

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.
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
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
Secondary acquired infection
The incidence of secondary acquired infections occurring within 2 months will be compared between the groups "immunosuppression" and "no immunosuppression".
mHLA-DR measurement
Evaluation of the immunological recovery at month 2 with regard to the initial state and in comparison with the controls.
Myeloid Derived Suppressor Cells (MDSC) measurement
Characterization of MDSC will be measured and compared between patient and control
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.
MDSC measurement
Characterization of MDSC will be measured
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.
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized and compared between patient and control.
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized and compared between patient and control.
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized

Full Information

First Posted
May 28, 2020
Last Updated
June 12, 2023
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT04438460
Brief Title
Pediatric Immune Response to Multi-Organ Dysfunction
Acronym
PedIMOD
Official Title
Pediatric Immune Response to Multi-Organ Dysfunction
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2020 (Actual)
Primary Completion Date
September 29, 2024 (Anticipated)
Study Completion Date
September 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Organ Dysfunction Syndrome
Keywords
Multiple organ dysfunction, Immunosuppression, mHLA-DR, Pediatrics, Secondary infection

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
210 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patient group
Arm Type
Experimental
Arm Description
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
Arm Title
Control group
Arm Type
Other
Arm Description
60 children aged 1 month to 12 years hospitalized for simple elective surgery will be included in this study
Intervention Type
Biological
Intervention Name(s)
Blood test
Intervention Description
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 Outcome Measure Information:
Title
mHLA-DR measurement
Description
The proportion of children with mHLA-DR < 8000 sites / cells on Day 3 - Day 5 will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months. The diagnosis of secondary acquired infection will be made by an independent committee.
Time Frame
Day 3
Secondary Outcome Measure Information:
Title
blood counts : Characterization of alterations in the myeloid lineage
Description
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time Frame
Day 1
Title
mHLA-DR expression : Characterization of alterations in the myeloid lineage
Description
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
Time Frame
Day 1
Title
transcriptome : Characterization of alterations in the myeloid lineage
Description
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.
Time Frame
Day 1
Title
plasma cytokines : Characterization of alterations in the myeloid lineage
Description
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time Frame
Day 1
Title
blood counts : Characterization of alterations in the myeloid lineage
Description
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months
Time Frame
Day 3
Title
mHLA-DR expression : Characterization of alterations in the myeloid lineage
Description
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.
Time Frame
Day 3
Title
transcriptome : Characterization of alterations in the myeloid lineage
Description
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.
Time Frame
Day 3
Title
plasma cytokines : Characterization of alterations in the myeloid lineage
Description
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time Frame
Day 3
Title
blood counts : Characterization of alterations in the myeloid lineage
Description
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time Frame
Day 60
Title
mHLA-DR expression : Characterization of alterations in the myeloid lineage
Description
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.
Time Frame
Day 60
Title
transcriptome : Characterization of alterations in the myeloid lineage
Description
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.
Time Frame
Day 60
Title
plasma cytokines : Characterization of alterations in the myeloid lineage
Description
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time Frame
Day 60
Title
Secondary acquired infection
Description
The incidence of secondary acquired infections occurring within 2 months will be compared between the groups "immunosuppression" and "no immunosuppression".
Time Frame
Day 60
Title
mHLA-DR measurement
Description
Evaluation of the immunological recovery at month 2 with regard to the initial state and in comparison with the controls.
Time Frame
Day 60
Title
Myeloid Derived Suppressor Cells (MDSC) measurement
Description
Characterization of MDSC will be measured and compared between patient and control
Time Frame
Day 1
Title
Intra-cellular production of tumor necrosis factor alpha (TNFα) by the monocyte
Description
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.
Time Frame
Day 1
Title
MDSC measurement
Description
Characterization of MDSC will be measured
Time Frame
Day 3
Title
Intra-cellular production of TNFα by the monocyte
Description
Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte.
Time Frame
Day 3
Title
Monocytic and dendritic subpopulations measurement
Description
Characterization of monocytic and dendritic subpopulations will be realized and compared between patient and control.
Time Frame
Day 1
Title
Gamma-delta T lymphocytes measurement
Description
Characterization of gamma-delta T lymphocytes will be realized and compared between patient and control.
Time Frame
Day 1
Title
Monocytic and dendritic subpopulations measurement
Description
Characterization of monocytic and dendritic subpopulations will be realized
Time Frame
Day 3
Title
Gamma-delta T lymphocytes measurement
Description
Characterization of gamma-delta T lymphocytes will be realized
Time Frame
Day 3
Title
Monocytic and dendritic subpopulations measurement
Description
Characterization of monocytic and dendritic subpopulations will be realized
Time Frame
Day 60
Title
Gamma-delta T lymphocytes measurement
Description
Characterization of gamma-delta T lymphocytes will be realized
Time Frame
Day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Solenn REMY, MD, PhD
Phone
0472 129 746
Ext
+33
Email
solene.remy@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Tiphanie Ginhoux
Phone
0427 857 723
Ext
+33
Email
tiphanie.ginhoux01@chu-lyon.fr
Facility Information:
Facility Name
Hôpital Femme Mère Enfant
City
Bron
ZIP/Postal Code
69500
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Solenn REMY, MD,PhD
Phone
0472 129 746
Ext
+33
Email
solene.remy@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Tiphanie Ginhoux
Phone
0427 857 723
Ext
+33
Email
tiphanie.ginhoux@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Solenn REMY, MD,PhD
First Name & Middle Initial & Last Name & Degree
Etienne JAVOUHEY, PU, PH
First Name & Middle Initial & Last Name & Degree
Dominique CHASSARD, PU, PH
Facility Name
Hopital Mère Enfant
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexis Chenouard, MD, PhD
Phone
02.40.08.34.83
Ext
+33
Email
Alexis.CHENOUARD@chu-nantes.fr
First Name & Middle Initial & Last Name & Degree
Alexis Chenouard, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

Pediatric Immune Response to Multi-Organ Dysfunction

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