COVID-19 by SARS-CoV-2 InfectionCoVInnateNCT04385017
Role of Inflammasomes in COVID-19 Disease
A study testing COVID-19 patients in people with COVID-19 by SARS-CoV-2 Infection, run by Centre Hospitalier Universitaire de Nice at 2 sites in France.
Trial summary
As of March 25, 2020, 414,179 cases and 18,440 deaths secondary to Coronavirus 2019 disease (COVID-19) have been reported worldwide. The unfavorable course of the patients is characterized on the immunological level by an intense pro-inflammatory response which can go as far as a cytokinic storm. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 by SARS-CoV-2 Infection
- What is being tested?
- COVID-19 patients
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 2 sitesFrance
- Study dates
- 11 May 2020to 30 Dec 2022
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age above 18 years old. SARS-CoV-2 infection confirmed by RT PCR or by serology Hospitalised patients with less than 14 days of COVID-19 symptoms. Date of first symptom being defined as to the date of one of the following symptoms : cough, dyspnea, fever above 38 °C, anosmia, dysgeusia or ageusia, chilblain Lupus erythematous Women of fertile age using at least one contraceptive method Health insurance Written informed consent
Who cannot join
- Pregnant or breastfeeding female
- Human immunodeficiency virus infection with CD4 under 200 cell/mm3
- Aplasia
- at-risk patients (minor, patient under judicial protection or tutorship)
Trial locations and contacts
2 sites in 1 country.
France2 sites
Ch Cannes, Réanimation
Cannes, Alpes Maritimes, 06
CHU de nice
Nice, Alpes-Maritimes, 06200
About this study
As of March 25, 2020, 414,179 cases and 18,440 deaths secondary to Coronavirus 2019 disease (COVID-19) have been reported worldwide. The unfavorable course of the patients is characterized on the immunological level by an intense pro-inflammatory response which can go as far as a cytokinic storm. This pandemic affects a naive world population from an immunological point of view with respect to SARS-CoV-2 responsible for COVID-19. The evolution is favorable without hospitalization in almost 85% of cases. Among patients hospitalized for pneumonia, some will not require ventilatory support while others will need intensive care. To date, two main types of unfavorable evolution have been described. The first is a bi-phasic evolution beginning with a paucisymptomatic form which is worsened secondarily with respiratory distress associated with a decrease in the viral load in the airways. The second is associated with persistent high viral loads in the airways and detection of the virus in the blood. These different clinical profiles could depend on the quantitative and qualitative response of the innate immune system.
At the early stage of a viral infection the innate immunity is capable of detecting certain conserved microbial patterns (PAMP, pathogen-associated molecular pattern) recognized by receptors dedicated to these patterns (PRR, pattern recognition receptor). This process allows to initiate the pro-inflammatory response via different signaling pathways.
Read more
Activating multiprotein complexes called inflammasomes, which cause pro-IL-1β and pro-IL-18 to be transformed into active pro-inflammatory cytokines are one of these pathways.
The central role of inflammasomes in the secretion of these pro-inflammatory cytokines deserves an in-depth study of their activation during COVID-19, whereas the inadequate inflammatory response appears to be the determining factor in the unfavorable development of patients.
The objective of this project is to analyze the level of activation of the inflammasomes and then to search for inactivating or activating mutations among the genes which code for the proteins constituting the inflammasomes in Covid-19 patients. The identification of mutations in patients with a serious clinical presentation or even death would be followed by fundamental work by analyzing in a cellular model the impact of these mutations on the secretion of IL-1β.
- Conditions
- COVID-19 by SARS-CoV-2 Infection
- Being tested
- COVID-19 patients
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
COVID-19 patientsOther
It will consist in the collection of 2 additional tubes at their blood draw. For DNA analysis, informed consent will be collected in writing
| Study group | Role | What they receive |
|---|---|---|
| DNA from monocytes | Other | It will consist in the collection of 2 additional tubes at their blood draw. For DNA analysis, informed consent will be collected in writing Receives: Other: COVID-19 patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of activation of inflammasomes in monocytes and polymorphonuclear neutrophils during COVID-19
Percentage of immune cells with inflammasome positive labeling using flow cytometry in comparison to controls
Measured: At inclusion
Secondary outcomes (1)
Genes nucleoside polymorphism analysis
Identification of genes nucleotide polymorphisms by Whole Exome Sequensing and bioinformatics analysis. Analysis of activating or inactivating mutations of NLRP3 NLRC4 AIM2 and Pyrin inflammasomes in patients with severe COVID-19.
Measured: At inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start11 May 2020
- Primary completion1 Feb 2022
- Study completion30 Dec 2022
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 COVID-19 by SARS-CoV-2 InfectionStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patient with COVID-19 disease
- Masking
- None (open label)
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- COURJON Johan, Principal investigator, CHU de Nice, Infectiologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04385017
- Sponsor's protocol ID
- 20-PP-07
- Acronym
- CoVInnate
- Status last verified
- Oct 2022
- First submitted
- 10 May 2020
- Last updated
- 22 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Courjon J, Dufies O, Robert A, Bailly L, Torre C, Chirio D, Contenti J, Vitale S, Loubatier C, Doye A, Pomares-Estran C, Gonfrier G, Lotte R, Munro P, Visvikis O, Dellamonica J, Giordanengo V, Carles M, Yvan-Charvet L, Ivanov S, Auberger P, Jacquel A, Boyer L. Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity. Blood Adv. 2021 Mar 9;5(5):1523-1534. doi: 10.1182/bloodadvances.2020003918.
PubMed 33683342
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Inflammasomes in COVID-19 Disease
- ClinicalTrials.gov ID
- NCT04385017
- Acronym / sponsor ID
- CoVInnate / 20-PP-07
- Conditions
- COVID-19 by SARS-CoV-2 Infection
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 11 May 2020 (actual)
- Primary completion
- 1 Feb 2022 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 12 May 2020 (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.
As of March 25, 2020, 414,179 cases and 18,440 deaths secondary to Coronavirus 2019 disease (COVID-19) have been reported worldwide. The unfavorable course of the patients is characterized on the immunological level by an intense pro-inflammatory response which can go as far as a cytokinic storm. This pandemic affects a naive world population from an immunological point of view with respect to SARS-CoV-2 responsible for COVID-19. The evolution is favorable without hospitalization in almost 85% of cases. Among patients hospitalized for pneumonia, some will not require ventilatory support while others will need intensive care. To date, two main types of unfavorable evolution have been described. The first is a bi-phasic evolution beginning with a paucisymptomatic form which is worsened secondarily with respiratory distress associated with a decrease in the viral load in the airways. The second is associated with persistent high viral loads in the airways and detection of the virus in the blood. These different clinical profiles could depend on the quantitative and qualitative response of the innate immune system.
At the early stage of a viral infection the innate immunity is capable of detecting certain conserved microbial patterns (PAMP, pathogen-associated molecular pattern) recognized by receptors dedicated to these patterns (PRR, pattern recognition receptor). This process allows to initiate the pro-inflammatory response via different signaling pathways.
Activating multiprotein complexes called inflammasomes, which cause pro-IL-1β and pro-IL-18 to be transformed into active pro-inflammatory cytokines are one of these pathways.
The central role of inflammasomes in the secretion of these pro-inflammatory cytokines deserves an in-depth study of their activation during COVID-19, whereas the inadequate inflammatory response appears to be the determining factor in the unfavorable development of patients.
The objective of this project is to analyze the level of activation of the inflammasomes and then to search for inactivating or activating mutations among the genes which code for the proteins constituting the inflammasomes in Covid-19 patients. The identification of mutations in patients with a serious clinical presentation or even death would be followed by fundamental work by analyzing in a cellular model the impact of these mutations on the secretion of IL-1β.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patient with COVID-19 disease
| Arm | Type | Receives |
|---|---|---|
| DNA from monocytes | Other | Other: COVID-19 patientsIt will consist in the collection of 2 additional tubes at their blood draw. For DNA analysis, informed consent will be collected in writing |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Age above 18 years old. SARS-CoV-2 infection confirmed by RT PCR or by serology Hospitalised patients with less than 14 days of COVID-19 symptoms. Date of first symptom being defined as to the date of one of the following symptoms : cough, dyspnea, fever above 38 °C, anosmia, dysgeusia or ageusia, chilblain Lupus erythematous Women of fertile age using at least one contraceptive method Health insurance Written informed consent
Key exclusion criteria (4 listed)
- Pregnant or breastfeeding female
- Human immunodeficiency virus infection with CD4 under 200 cell/mm3
- Aplasia
- at-risk patients (minor, patient under judicial protection or tutorship)
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 |
|---|---|---|
| COVID-19 patientsIt will consist in the collection of 2 additional tubes at their blood draw. For DNA analysis, informed consent will be collected in writing | Other | DNA from monocytes |
Primary outcome
Level of activation of inflammasomes in monocytes and polymorphonuclear neutrophils during COVID-19
Time frame: At inclusion
Percentage of immune cells with inflammasome positive labeling using flow cytometry in comparison to controls
1 secondary outcome
Genes nucleoside polymorphism analysis
Time frame: At inclusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2023.
- Derived from this study: PubMed 33683342Courjon J, Dufies O, Robert A, Bailly L, Torre C, Chirio D, Contenti J, Vitale S, Loubatier C, Doye A, Pomares-Estran C, Gonfrier G, Lotte R, Munro P, Visvikis O, Dellamonica J, Giordanengo V, Carles M, Yvan-Charvet L, Ivanov S, Auberger P, Jacquel A, Boyer L. Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity. Blood Adv. 2021 Mar 9;5(5):1523-1534. doi: 10.1182/bloodadvances.2020003918.
- Individual participant dataSharing planned: Undecided
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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.
COURJON Johan principal investigator
CHU de Nice, Infectiologie
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing COVID-19 patients in people with COVID-19 by SARS-CoV-2 Infection, run by Centre Hospitalier Universitaire de Nice at 2 sites 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 1 inclusion and 4 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: finished, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Level of activation of inflammasomes in monocytes and polymorphonuclear neutrophils during COVID-19 (time frame: At inclusion). 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 NCT04385017, 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 22 Mar 2023.