Back to resultsImpact of Bacterial Expression and Immune Response in the Severity of Pertussis (PERT-SEVEREII)
Primary Purpose
Bordetella Pertussis, Whooping Cough
Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Nasopharyngeal swab
Blood samples
Sponsored by
About this trial
This is an interventional basic science trial for Bordetella Pertussis, Whooping Cough focused on measuring vaccination
Eligibility Criteria
Inclusion Criteria: be between the ages of 0 and 15 years inclusive be suspected of having pertussis by the physician in charge, with the prescription of a diagnostic PCR (pertussis PCR, which may be a syndromic PCR, a PCR targeting IS481 and/or IS1001) be free of any pathology/treatment that may influence the immune response (autoimmune/inflammatory pathology or immune deficiency not listed above, hepatic insufficiency, taking immunosuppressive treatment (including taking oral corticosteroids with a dose ≥ 10 mg/d Prednisone equivalent for more than 15 days) Have received age-appropriate information and written assent or consent from their parents/legal guardians be affiliated with or benefiting from a social security plan Exclusion Criteria: Patient with any pathology/treatment that may influence the immune response (autoimmune/inflammatory pathology or immune deficiency not listed above, hepatic failure, taking immunosuppressive therapy (including oral corticosteroids with dose ≥ 10 mg/d prednisone equivalent for more than 15 days) Use of antibiotics active against pertussis in the 24 hours preceding the sampling Delay between the result of the diagnostic sample (pertussis PCR) and the day of inclusion > 48 hours Patient's condition that, in the opinion of the physician, is incompatible with the expanded/additional sampling(s) required by the study Infant with a weight < 2.5 kg at the time of inclusion.
Sites / Locations
- CHU de Bordeaux
- Hôpital Louis Mourier
- Centre hospitalier intercommunal de Créteil
- Hôpital Roger Salengo
- Hospices Civils de Lyon
- Hôpital de la Timone Enfants, APHM
- Hôpital Nord, APHM
- CHU de Nantes
- CHU Armand Trousseau
- Hopital Necker
- Hôpital Robert Debré
- CHU Rouen
- Réseau ACTIV
- CHU de Toulouse
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Children between 0 and 15 years with suspected pertussis
Arm Description
Outcomes
Primary Outcome Measures
Measurement of expression level of Bp genes during infection by Nanostring transcriptomic analysis of Bp isolates from the nasopharynx of children with pertussis.
To identify in a standardized way the microbial "in situ" expression profiles of currently circulating Bp genes during infection in children ;
Measurement of plasma cytokine and chemokine concentrations by SIMOA digital ELISA
To determine systemic and respiratory immune responses in children during pertussis.
Phenotyping of immune cells by cytometry with a 20-color flow cytometry panel
To determine systemic and respiratory immune responses in children during pertussis.
Secondary Outcome Measures
Measurement of expression level of Bp genes which is modified by recent gene developments related to vaccine pressure by Nanostring transcriptomic analysis of Bp isolates
List of microbial genes which expression is modified by recent genomic developments related to vaccine pressure
Measurement of high expression level of Bp genes in all clinical forms of pertussis by Nanostring transcriptomic analysis of Bp isolates
To identify new candidate Bp genes for a future protein vaccine
Measurement of expression level of Bp genes which is associated with severe pertussis by Nanostring transcriptomic analysis of Bp isolates
List of virulence genes differentially expressed during severe pertussis
Full Information
NCT ID
NCT05897879
First Posted
May 22, 2023
Last Updated
June 1, 2023
Sponsor
Institut Pasteur
Collaborators
Hôpital Necker-Enfants Malades, Hospices Civils de Lyon, Hopital Universitaire Robert-Debre, Centre Hospitalier Intercommunal Creteil, Nantes University Hospital, Réseau ACTIV, Hôpital Armand Trousseau, CHR - Hôpital Roger Salengo, Hôpital Nord - APHM, Hôpital Louis Mourier, University Hospital, Toulouse, University Hospital, Bordeaux, Hôpital de la Timone, University Hospital, Rouen
1. Study Identification
Unique Protocol Identification Number
NCT05897879
Brief Title
Impact of Bacterial Expression and Immune Response in the Severity of Pertussis
Acronym
PERT-SEVEREII
Official Title
Impact of Bacterial Expression and Immune Response in the Severity of Pertussis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
July 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Pasteur
Collaborators
Hôpital Necker-Enfants Malades, Hospices Civils de Lyon, Hopital Universitaire Robert-Debre, Centre Hospitalier Intercommunal Creteil, Nantes University Hospital, Réseau ACTIV, Hôpital Armand Trousseau, CHR - Hôpital Roger Salengo, Hôpital Nord - APHM, Hôpital Louis Mourier, University Hospital, Toulouse, University Hospital, Bordeaux, Hôpital de la Timone, University Hospital, Rouen
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
The resurgence of pertussis is associated with an evolutionary mechanism under the pressure of current acellular vaccines, with a possible impact on vaccine effectiveness and disease expression. Little is known about the mechanisms involved in the clinical variability of pertussis, including its most severe malignant form observed in infants (mortality between 50-80%). The main challenges are: (i) the lack of knowledge about the gene expression of B. pertussis strains currently circulating during human infection, incorporating evolutionary changes and vaccine-induced selective pressure; (ii) the poor understanding of the variability in clinical expression of pertussis, and (iii) the lack of biomarkers to predict disease severity or prognosis in infants.
An integrative strategy combining a clinical, microbiological, immunological and 'omic' approach from a prospective cohort of children with pertussis will be used to identify
'in situ' expression profiles of B. pertussis genes and proteins incorporating recent evolutionary changes and
a systemic and respiratory immune signature in B. pertussis-infected children according to severity.
Results should furthermore serve as a prerequisite for the identification of severity biomarkers and new vaccine antigen candidates taking into account specific immune responses in infants.
Detailed Description
The study design is characterized by 4 work packages:
Collection of clinical data and biological samples (deep nasal swab, blood sample) from children with pertussis
Construction and validation of a microbial panel of 200 genes of interest (involved in virulence and/or potential vaccine antigens) for transcriptomic analysis
Transcriptomic study using the panel of interest of B. pertussis isolates from nasopharyngeal swabs preserved with an RNA stabilizer, using the Nanostring® technique
Study of the immune response during pertussis
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bordetella Pertussis, Whooping Cough
Keywords
vaccination
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
210 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Children between 0 and 15 years with suspected pertussis
Arm Type
Other
Intervention Type
Biological
Intervention Name(s)
Nasopharyngeal swab
Intervention Description
For hospitalized patients :
Nasopharyngeal swab (1 aspiration or 2 swabs (1 in each nostril))
For ambulatory patients :
Deep nasal swab: 2 swabs (1 in each nostril), or 1 swab only for children for whom taking 2 swabs is complicated.
Intervention Type
Biological
Intervention Name(s)
Blood samples
Intervention Description
For hospitalized patients : 3 to 7.5 ml For ambulatory patients: Fingertip blood sampling
Primary Outcome Measure Information:
Title
Measurement of expression level of Bp genes during infection by Nanostring transcriptomic analysis of Bp isolates from the nasopharynx of children with pertussis.
Description
To identify in a standardized way the microbial "in situ" expression profiles of currently circulating Bp genes during infection in children ;
Time Frame
3 years
Title
Measurement of plasma cytokine and chemokine concentrations by SIMOA digital ELISA
Description
To determine systemic and respiratory immune responses in children during pertussis.
Time Frame
3 years
Title
Phenotyping of immune cells by cytometry with a 20-color flow cytometry panel
Description
To determine systemic and respiratory immune responses in children during pertussis.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Measurement of expression level of Bp genes which is modified by recent gene developments related to vaccine pressure by Nanostring transcriptomic analysis of Bp isolates
Description
List of microbial genes which expression is modified by recent genomic developments related to vaccine pressure
Time Frame
3 years
Title
Measurement of high expression level of Bp genes in all clinical forms of pertussis by Nanostring transcriptomic analysis of Bp isolates
Description
To identify new candidate Bp genes for a future protein vaccine
Time Frame
3 years
Title
Measurement of expression level of Bp genes which is associated with severe pertussis by Nanostring transcriptomic analysis of Bp isolates
Description
List of virulence genes differentially expressed during severe pertussis
Time Frame
3 years
10. Eligibility
Sex
All
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
be between the ages of 0 and 15 years inclusive
be suspected of having pertussis by the physician in charge, with the prescription of a diagnostic PCR (pertussis PCR, which may be a syndromic PCR, a PCR targeting IS481 and/or IS1001)
be free of any pathology/treatment that may influence the immune response (autoimmune/inflammatory pathology or immune deficiency not listed above, hepatic insufficiency, taking immunosuppressive treatment (including taking oral corticosteroids with a dose ≥ 10 mg/d Prednisone equivalent for more than 15 days)
Have received age-appropriate information and written assent or consent from their parents/legal guardians
be affiliated with or benefiting from a social security plan
Exclusion Criteria:
Patient with any pathology/treatment that may influence the immune response (autoimmune/inflammatory pathology or immune deficiency not listed above, hepatic failure, taking immunosuppressive therapy (including oral corticosteroids with dose ≥ 10 mg/d prednisone equivalent for more than 15 days)
Use of antibiotics active against pertussis in the 24 hours preceding the sampling
Delay between the result of the diagnostic sample (pertussis PCR) and the day of inclusion > 48 hours
Patient's condition that, in the opinion of the physician, is incompatible with the expanded/additional sampling(s) required by the study
Infant with a weight < 2.5 kg at the time of inclusion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julie Toubiana, MD
Phone
+331 45 68 80 05
Email
julie.toubiana@pasteur.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie Toubiana, MD
Organizational Affiliation
Institut Pasteur
Official's Role
Study Director
Facility Information:
Facility Name
CHU de Bordeaux
City
Bordeaux
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emilie Pauquet, MD
Facility Name
Hôpital Louis Mourier
City
Colombes
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain Basmaci, MD
Facility Name
Centre hospitalier intercommunal de Créteil
City
Créteil
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fouad Madhi, MD
Facility Name
Hôpital Roger Salengo
City
Lille
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
François Dubos, MD
Facility Name
Hospices Civils de Lyon
City
Lyon
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine Ouziel, MD
Facility Name
Hôpital de la Timone Enfants, APHM
City
Marseille
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurélie Morand, MD
Facility Name
Hôpital Nord, APHM
City
Marseille
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Minodier, MD
Facility Name
CHU de Nantes
City
Nantes
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Malorey, MD
Facility Name
CHU Armand Trousseau
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mathie Lorrot, MD
Facility Name
Hopital Necker
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Toubiana, MD
Facility Name
Hôpital Robert Debré
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Albert Faye, MD
Facility Name
CHU Rouen
City
Rouen
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Didier Pinquier, MD
Facility Name
Réseau ACTIV
City
Saint-Maur-des-Fossés
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Cohen, MD
Facility Name
CHU de Toulouse
City
Toulouse
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Camille Brehin, MD
12. IPD Sharing Statement
Learn more about this trial
Impact of Bacterial Expression and Immune Response in the Severity of Pertussis
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