Meningitis EnterovirusBledi-CytokineNCT04711876
Characterization of Cytokines Expression During Enterovirus Meningitis in Paediatric Populations.
An observational study of Meningitis Enterovirus, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
Enteroviruses (EV) are the most frequent cause of acute meningitis in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by Polymerase Chain Reaction (PCR) is the gold standard diagnostic test. Read more about this study
- Who is it for?
- Ages 1 day to 16 years
- Conditions the study is for
- Meningitis Enterovirus
- What is being tested?
- Cytokine level in blood and CSF
- How many people
- 180 participants
- Where
- 1 siteFrance
- Study dates
- 1 Apr 2021to 1 Jun 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 16 years
- All sexes
- Child
Study population: Paediatric patient with suspicion of meningitis
Who may be able to join
- Patients with proven enterovirus meningitis (RT- PCR EV positive)
- Control patients admitted for suspected meningitis infection but for whom the bacteriological (LCS culture/ blood culture negative) and virological diagnosis (testing for enteroviruses (RT-PCR negative) and parechoviruses (viruses responsible for symptoms similar to those of EVs) is negative
Who cannot join
- For patients with EV meningitis, we will exclude:
- patients with co-infection
- haemorrhagic CSF samples
- samples (CSF or blood) for which we do not have access to EV viral load results
- samples (CSF or blood) for which we do not have access to the EV genotyping results
- For patients in the control group (without EV meningitis), we will exclude :
Show all 10Show fewer
- Samples from patients with an infection (viral or bacterial) in the control group.
- haemorrhagic CSF samples
- CSF samples with pleocytosis (presence of CSF leucocytes).
- Blood samples with high CRP (CRP>15mg/L).
Trial locations and contacts
1 site in 1 country.
France1 site
University Hospital, Clermont Ferrand
Clermont-Ferrand, AURA, 63000
Christine ARCHIMBAUD
About this study
Official title: Study of the Inflammatory Response to Enterovirus Meningitis in Newborns, Infants and Children, as Assessed by Cytokine Levels in Blood and Cerebrospinal Fluid. Case-control Comparison Using an Existing Cohort.
Enteroviruses (EV) are the most frequent cause of acute meningitis in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by Polymerase Chain Reaction (PCR) is the gold standard diagnostic test. Recently, our laboratory published the BLEDI study which highlighted the interest of detecting EV in the blood of the paediatric population : (i) EV was found in more than a quarter of cases in the blood of infants admitted to hospital with isolated fever and (ii) detection of EV was more frequent in the blood than in CSF in neonates and infants with isolated fever, sepsis or meningitis. However, the pathophysiology of EV infections is poorly understood and little work has been done on the inflammatory response to these infections. In EV meningitis, the inflammatory response has been studied primarily in children infected with enterovirus A71 (EV-A71). Indeed, in these children, inappropriate cytokine secretion (cytokine storm) leads to severe neurological and cardiopulmonary damage, which can progress to death. The study of the inflammatory response during meningitis due to other types of EV remains poorly
The objective of BLEDI-CYTOKINES (ancillary study of the BLEDI study) is to study the inflammatory response during EV meningitis in neonates, infants and children, as assessed by cytokine levels in blood and cerebrospinal fluid, by comparing case-controls from an existing cohort.
Read the detailed description
EVs are characterized by their high genetic variability, with more than 120 types described to date. They are involved in mild infections, such as febrile syndromes that may be associated with respiratory and cutaneous manifestations. However, these viruses are also involved in more severe infections of the nervous system. In children infected with EV-A71, which causes mild epidemics of foot-and-mouth disease, inappropriate cytokine secretion (cytokine storm) leads to severe neurological and cardiopulmonary complications that can progress to death in children (<5 years of age) in Asia. Many studies have focused on the inflammatory response to EV-A71 infections: some cytokines (Tumor Necrose Factor (TNF), INterFeron (INF), InterLeukine (IL)1, IL6, IL10, eotaxin,...) dosed in CSF have been associated with severe EV-A71 infections (2,5,6). Recently, a Japanese study showed an overexpression of IL-6 in the blood of children with EV-A71 foot-hand-mouth syndrome. The authors defined that a level of IL-6 ≥ 66 pg/mL could be a prognostic marker of progression to aseptic meningitis (6). In EV (other than EV-A71) meningitis, pro-inflammatory cytokines such as IL6, IL8, and INF are produced in the acute phase in CSF to control the infection, and then they decline and anti-inflammatory cytokines such as IL10 are synthesized (7). In addition, studies have shown that the production of some cytokines is greater in severe EV infections: for example, the production of IL4 and IL5 is greater in EV encephalitis than in EV skin infections (8).
However, there are very few comparative studies of cytokine expression in blood and CSF. In addition, little work has been done to study cytokine expression in meningitis due to EV other than EV-A71. In young children, these meningitis may also be complicated by encephalitis, myelitis, and even flaccid paralysis (including poliomyelitis) (2-4). The pathophysiology of these severe EV infections is currently unknown. In addition, no preventive vaccine is available against these infections (other than polio vaccine), nor are there effective curative antivirals for severe EV infections.
- Conditions
- Meningitis Enterovirus
- Being tested
- Cytokine level in blood and CSF
- Keywords
- Enterovirus infection, Cytokine expression, Paediatric population, Blood, Cerebrospinal fluid, Inflammatory, Meningitis viral
- Medical subject headings
- Enterovirus Infections, Meningitis, Viral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytokine level in blood and CSFBiological
Measure of cytokine level
| Study group | Role | What they receive |
|---|---|---|
| Test group with enterovirus meningitis | Level of Cytokine in blood and CSF for Patient with RT-PCR-EV + Receives: Biological: Cytokine level in blood and CSF | |
| Control group with no enterovirus meningitis | Level of Cytokine in blood and CSF for Patient with RT-PCR-EV - Receives: Biological: Cytokine level in blood and CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression of cytokine in blood
Level of cytokine in blood
Measured: Day 1
Expression of cytokine in cerebrospinal fluid
Level of cytokine in cerebrospinal fluid
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2021
- Study start1 Apr 2021 (estimated)
- Primary completion1 Jun 2021 (estimated)
- Study completion1 Jun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Meningitis EnterovirusStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Collaborators
- Laboratory of virology, National Enterovirus and parechovirus Reference Center, University Hospital of Clermont-Ferrand
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04711876
- Sponsor's protocol ID
- 2020 ARCHIMBAUD Bledi-Cytokine
- Acronym
- Bledi-Cytokine
- Status last verified
- Jan 2021
- First submitted
- 13 Jan 2021
- Last updated
- 15 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lafolie J, Labbe A, L'Honneur AS, Madhi F, Pereira B, Decobert M, Adam MN, Gouraud F, Faibis F, Arditty F, Marque-Juillet S, Guitteny MA, Lagathu G, Verdan M, Rozenberg F, Mirand A, Peigue-Lafeuille H, Henquell C, Bailly JL, Archimbaud C; Blood Enterovirus Diagnosis Infection (BLEDI) in paediatric population study team. Assessment of blood enterovirus PCR testing in paediatric populations with fever without source, sepsis-like disease, or suspected meningitis: a prospective, multicentre, observational cohort study. Lancet Infect Dis. 2018 Dec;18(12):1385-1396. doi: 10.1016/S1473-3099(18)30479-1. Epub 2018 Oct 30.
PubMed 30389482
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Inflammatory Response to Enterovirus Meningitis in Newborns, Infants and Children, as Assessed by Cytokine Levels in Blood and Cerebrospinal Fluid. Case-control Comparison Using an Existing Cohort.
- ClinicalTrials.gov ID
- NCT04711876
- Acronym / sponsor ID
- Bledi-Cytokine / 2020 ARCHIMBAUD Bledi-Cytokine
- Conditions
- Meningitis Enterovirus
- Keywords
- Enterovirus infection, Cytokine expression, Paediatric population, Blood, Cerebrospinal fluid, Inflammatory, Meningitis viral
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Collaborators
- Laboratory of virology, National Enterovirus and parechovirus Reference Center, University Hospital of Clermont-Ferrand
- Study start
- 1 Apr 2021 (estimated)
- Primary completion
- 1 Jun 2021 (estimated)
- Study completion
- 1 Jun 2021 (estimated)
- First posted
- 15 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Enteroviruses (EV) are the most frequent cause of acute meningitis in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by Polymerase Chain Reaction (PCR) is the gold standard diagnostic test. Recently, our laboratory published the BLEDI study which highlighted the interest of detecting EV in the blood of the paediatric population : (i) EV was found in more than a quarter of cases in the blood of infants admitted to hospital with isolated fever and (ii) detection of EV was more frequent in the blood than in CSF in neonates and infants with isolated fever, sepsis or meningitis. However, the pathophysiology of EV infections is poorly understood and little work has been done on the inflammatory response to these infections. In EV meningitis, the inflammatory response has been studied primarily in children infected with enterovirus A71 (EV-A71). Indeed, in these children, inappropriate cytokine secretion (cytokine storm) leads to severe neurological and cardiopulmonary damage, which can progress to death. The study of the inflammatory response during meningitis due to other types of EV remains poorly
The objective of BLEDI-CYTOKINES (ancillary study of the BLEDI study) is to study the inflammatory response during EV meningitis in neonates, infants and children, as assessed by cytokine levels in blood and cerebrospinal fluid, by comparing case-controls from an existing cohort.
Detailed description
EVs are characterized by their high genetic variability, with more than 120 types described to date. They are involved in mild infections, such as febrile syndromes that may be associated with respiratory and cutaneous manifestations. However, these viruses are also involved in more severe infections of the nervous system. In children infected with EV-A71, which causes mild epidemics of foot-and-mouth disease, inappropriate cytokine secretion (cytokine storm) leads to severe neurological and cardiopulmonary complications that can progress to death in children (<5 years of age) in Asia. Many studies have focused on the inflammatory response to EV-A71 infections: some cytokines (Tumor Necrose Factor (TNF), INterFeron (INF), InterLeukine (IL)1, IL6, IL10, eotaxin,...) dosed in CSF have been associated with severe EV-A71 infections (2,5,6). Recently, a Japanese study showed an overexpression of IL-6 in the blood of children with EV-A71 foot-hand-mouth syndrome. The authors defined that a level of IL-6 ≥ 66 pg/mL could be a prognostic marker of progression to aseptic meningitis (6). In EV (other than EV-A71) meningitis, pro-inflammatory cytokines such as IL6, IL8, and INF are produced in the acute phase in CSF to control the infection, and then they decline and anti-inflammatory cytokines such as IL10 are synthesized (7). In addition, studies have shown that the production of some cytokines is greater in severe EV infections: for example, the production of IL4 and IL5 is greater in EV encephalitis than in EV skin infections (8).
However, there are very few comparative studies of cytokine expression in blood and CSF. In addition, little work has been done to study cytokine expression in meningitis due to EV other than EV-A71. In young children, these meningitis may also be complicated by encephalitis, myelitis, and even flaccid paralysis (including poliomyelitis) (2-4). The pathophysiology of these severe EV infections is currently unknown. In addition, no preventive vaccine is available against these infections (other than polio vaccine), nor are there effective curative antivirals for severe EV infections.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test group with enterovirus meningitis | – | Biological: Cytokine level in blood and CSFLevel of Cytokine in blood and CSF for Patient with RT-PCR-EV + |
| Control group with no enterovirus meningitis | – | Biological: Cytokine level in blood and CSFLevel of Cytokine in blood and CSF for Patient with RT-PCR-EV - |
Who may qualify
- Ages
- 1 day to 16 years
- Sex
- All
- Age groups
- Child
- Study population
- Paediatric patient with suspicion of meningitis
Key inclusion criteria (2 listed)
- Patients with proven enterovirus meningitis (RT- PCR EV positive)
- Control patients admitted for suspected meningitis infection but for whom the bacteriological (LCS culture/ blood culture negative) and virological diagnosis (testing for enteroviruses (RT-PCR negative) and parechoviruses (viruses responsible for symptoms similar to those of EVs) is negative
Key exclusion criteria (10 listed)
- patients with co-infection
- haemorrhagic CSF samples
- samples (CSF or blood) for which we do not have access to EV viral load results
- samples (CSF or blood) for which we do not have access to the EV genotyping results
- Samples from patients with an infection (viral or bacterial) in the control group.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytokine level in blood and CSFMeasure of cytokine level | Biological | Control group with no enterovirus meningitis, Test group with enterovirus meningitis |
Primary outcome
Expression of cytokine in blood
Time frame: Day 1
Level of cytokine in blood
Expression of cytokine in cerebrospinal fluid
Time frame: Day 1
Level of cytokine in cerebrospinal fluid
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2021.
- Background: PubMed 30389482Lafolie J, Labbe A, L'Honneur AS, Madhi F, Pereira B, Decobert M, Adam MN, Gouraud F, Faibis F, Arditty F, Marque-Juillet S, Guitteny MA, Lagathu G, Verdan M, Rozenberg F, Mirand A, Peigue-Lafeuille H, Henquell C, Bailly JL, Archimbaud C; Blood Enterovirus Diagnosis Infection (BLEDI) in paediatric population study team. Assessment of blood enterovirus PCR testing in paediatric populations with fever without source, sepsis-like disease, or suspected meningitis: a prospective, multicentre, observational cohort study. Lancet Infect Dis. 2018 Dec;18(12):1385-1396. doi: 10.1016/S1473-3099(18)30479-1. Epub 2018 Oct 30.
Related trials for Meningitis Enterovirus
RecruitingObservational study
Risk Assessment of Community Spread of Multiple Endemic Infectious Diseases in a One Health Perspective
Dengue, Chikungunya
Active, not recruitingObservational study
Molecular Epidemiology of Enteroviruses Detected at the Virology Laboratory of Brest University Hospital During the Period 2018-2024: Retrospective Analysis of an Atypical Meningitis Epidemic in 2024 (BrEcho9Men)
Enterovirus Infections, Meningitis, Viral
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Meningitis Enterovirus, run by University Hospital, Clermont-Ferrand at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lise Laclautre (0473754963, promo_interne_drci@chu-clermontferrand.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Expression of cytokine in blood (time frame: Day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04711876, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2021.