Disease, ViralResistirNCT04403061
Th1/Th2/Th17/TREG and TLRs Activation/KIR for COVID 19 Prediction of Outcome
An observational study of Disease, Viral and Cytokine Release Syndrome, run by Asociacion para el Estudio de las Enfermedades Infecciosas at 1 site in Spain.
Trial summary
To ascertain globally the changes in the cytokines involved and TLRs/KIR activation in patients admitted to the hospital with a COVID-19 diagnosis, and the changes after initiation of the different therapies Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Disease, Viral, Cytokine Release Syndrome, TLRs
- What is being tested?
- Cytokines measurement, Cellular response and TLRs activation measurement
- How many people
- 106 participants
- Where
- 1 siteSpain
- Study dates
- 22 May 2020to 10 Jan 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 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a diagnosis of COVID-19
Who may be able to join
- Patients with a diagnosis of COVID-19 (PCR confirmed)
Who cannot join
- No informed consent
- Presence of chronic therapy with immunomodulators, corticoids or antineoplastic agents.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Th1/Th2/Th17/TREG Response and TLRs Activation/KIR Receptors for Predicting the Evolution of the SARS Cov-2 Infected Patients
To ascertain globally the changes in the cytokines involved and TLRs/KIR activation in patients admitted to the hospital with a COVID-19 diagnosis, and the changes after initiation of the different therapies
Read the detailed description
COVID-19 is a disease with an initial viral phase followed, usually at the 7th day, of an inflammatory state (cytokine storm) leading to respiratory distress, ICU admission and risk of death. Thus, several biological agents, antagonists of the different cytokines (IL-6, IL-1) have been used for patients with severe disease. However, there are no data about the cytokine changes, at admission and after therapy, and its predictive value, a fundamental knowledge to establish the best therapeutic strategy.
The first line of immune defense is the interaction of the virus with innate immunity cell members. The toll like receptors (TLRs) family is a group of pattern recognition receptors that include many different molecules (21-23). These bindings can activate dendritic cells, monocytes, macrophages. There is an important RNA and DNA connection, activation of TLRs, the production of type I interferons, and the development of some autoimmune diseases. TLR7 and TLR8 specifically recognize simple-chain RNA of viruses and are expressed in endosomal membranes. TLR8 is expressed in regulatory cells (Treg) and its activation results in inhibition of its regulatory functions. Natural killer cells (NK) respond to alterations of class I HLA molecules present in infected cells (24-26). An increase in class I HLA expression could lead to an increase in NK activation by increasing its ability to produce IFN-gamma. Therefore, the reasons for KIR binding are often variable between individuals and between populations.
- Conditions
- Disease, Viral, Cytokine Release Syndrome, TLRs
- Being tested
- Cytokines measurement, Cellular response, TLRs activation measurement, KIR phenotype evaluation
- Medical subject headings
- Virus Diseases, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytokines measurementDiagnostic test
Quantification of plasma cytokine levels of human GM-CSF, IFN-α, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-17A, and TNF-α using multiplex technol-ogy (quantitative measure).
Cellular responseDiagnostic test
SARS-CoV-2 peptides (Prot-S, Pros-N and Port-M) will be used to activate CD4 and CD8 T cells. Cytokines released, such as IFNg, TNFa, IL4, IL17A, and IL2, from each cell subset will be measured by flow cytometry (quantitative measure).
TLRs activation measurementDiagnostic test
After specific cell activation through TLR7/8 receptors, such as resiquimod, ORN R-0002, ORN R-0006, ORN R-1263, ORN R-2336, and controls as Poly (I:C), the release of IFNa, IFNg, TNFa, IL12, and IL6 will be analyzed (quantitative measure).
KIR phenotype evaluationDiagnostic test
Characterization of the presence of 14 genes plus 2 pseudogenes of KIR gene family (qualitative genotyping) by PCR, mRNA expression profiling (quantitative measures) by RT-PCR, and phenotyping of human NK cells analyzing different KIR receptors (quantitative measure) by flow cytometry, will be analyzed.
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in cytokines associated with SARS CoV-2 infection
Measured: 1 month
Evaluation of cellular response
Measured: 1 month
TLRs activation
Measured: 1 month
KIR phenotype determination
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start22 May 2020
- Primary completion22 Dec 2020
- Study completion10 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Disease, ViralStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asociacion para el Estudio de las Enfermedades Infecciosas
- Sponsor type
- Research network
- Collaborators
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04403061
- Sponsor's protocol ID
- EC128/20
- Acronym
- Resistir
- Status last verified
- Jan 2021
- First submitted
- 23 May 2020
- Last updated
- 12 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Pending to establish collaboration to share cytokine measurements
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Th1/Th2/Th17/TREG Response and TLRs Activation/KIR Receptors for Predicting the Evolution of the SARS Cov-2 Infected Patients
- ClinicalTrials.gov ID
- NCT04403061
- Acronym / sponsor ID
- Resistir / EC128/20
- Conditions
- Disease, Viral, Cytokine Release Syndrome, TLRs
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Asociacion para el Estudio de las Enfermedades InfecciosasResearch network
- Collaborators
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Study start
- 22 May 2020 (actual)
- Primary completion
- 22 Dec 2020 (actual)
- Study completion
- 10 Jan 2021 (actual)
- First posted
- 27 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.
To ascertain globally the changes in the cytokines involved and TLRs/KIR activation in patients admitted to the hospital with a COVID-19 diagnosis, and the changes after initiation of the different therapies
Detailed description
COVID-19 is a disease with an initial viral phase followed, usually at the 7th day, of an inflammatory state (cytokine storm) leading to respiratory distress, ICU admission and risk of death. Thus, several biological agents, antagonists of the different cytokines (IL-6, IL-1) have been used for patients with severe disease. However, there are no data about the cytokine changes, at admission and after therapy, and its predictive value, a fundamental knowledge to establish the best therapeutic strategy.
The first line of immune defense is the interaction of the virus with innate immunity cell members. The toll like receptors (TLRs) family is a group of pattern recognition receptors that include many different molecules (21-23). These bindings can activate dendritic cells, monocytes, macrophages. There is an important RNA and DNA connection, activation of TLRs, the production of type I interferons, and the development of some autoimmune diseases. TLR7 and TLR8 specifically recognize simple-chain RNA of viruses and are expressed in endosomal membranes. TLR8 is expressed in regulatory cells (Treg) and its activation results in inhibition of its regulatory functions. Natural killer cells (NK) respond to alterations of class I HLA molecules present in infected cells (24-26). An increase in class I HLA expression could lead to an increase in NK activation by increasing its ability to produce IFN-gamma. Therefore, the reasons for KIR binding are often variable between individuals and between populations.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a diagnosis of COVID-19
Key inclusion criteria (1 listed)
- Patients with a diagnosis of COVID-19 (PCR confirmed)
Key exclusion criteria (2 listed)
- No informed consent
- Presence of chronic therapy with immunomodulators, corticoids or antineoplastic agents.
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 |
|---|---|---|
| Cytokines measurementQuantification of plasma cytokine levels of human GM-CSF, IFN-α, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-17A, and TNF-α using multiplex technol-ogy (quantitative measure). | Diagnostic test | – |
| Cellular responseSARS-CoV-2 peptides (Prot-S, Pros-N and Port-M) will be used to activate CD4 and CD8 T cells. Cytokines released, such as IFNg, TNFa, IL4, IL17A, and IL2, from each cell subset will be measured by flow cytometry (quantitative measure). | Diagnostic test | – |
| TLRs activation measurementAfter specific cell activation through TLR7/8 receptors, such as resiquimod, ORN R-0002, ORN R-0006, ORN R-1263, ORN R-2336, and controls as Poly (I:C), the release of IFNa, IFNg, TNFa, IL12, and IL6 will be analyzed (quantitative measure). | Diagnostic test | – |
| KIR phenotype evaluationCharacterization of the presence of 14 genes plus 2 pseudogenes of KIR gene family (qualitative genotyping) by PCR, mRNA expression profiling (quantitative measures) by RT-PCR, and phenotyping of human NK cells analyzing different KIR receptors (quantitative measure) by flow cytometry, will be analyzed. | Diagnostic test | – |
Primary outcome
Changes in cytokines associated with SARS CoV-2 infection
Time frame: 1 month
Evaluation of cellular response
Time frame: 1 month
TLRs activation
Time frame: 1 month
KIR phenotype determination
Time frame: 1 month
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 12 Jan 2021.
- Individual participant dataSharing planned: Undecided. Pending to establish collaboration to share cytokine measurements
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Disease, Viral and Cytokine Release Syndrome, run by Asociacion para el Estudio de las Enfermedades Infecciosas at 1 site in Spain.
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 2 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 12 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 Spain. 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?
Changes in cytokines associated with SARS CoV-2 infection (time frame: 1 month). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jan 2021.