Covid19NCT04646239
Biomarkers of Trained Immunity Following MMR Vaccination
An observational study of Covid19, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This is a substudy of NCT04333732. The goal of this sub-study is to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially viral associated products, in the MMR vaccinated compared placebo groups. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Covid19
- What is being tested?
- Heterologous stimuli and Neutralization assay
- Type of treatment
- Vaccines, Injection or infusion
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2020to 28 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The CROWN CORONATION trial enrolls adults at risk of developing COVID-19 due to their work in the healthcare environment. To be eligible, prospective participants for the CROWN CORONATION trial must not have a contra-indication to receiving the live attenuated Measles, Mumps and Rubella vaccine (MMR) and must not be exposed to agents that may complicate the interpretation of findings regarding the hypothesized protective effect of MMR for the prevention of COVID-19. The sub-study will consecutively approach all participants enrolled in the CROWN CORONATION trial to elicit enrolment in the sub-study cohort.
Who may be able to join
- Prospective participant must already be enrolled into the CROWN CORONATION trial at the sub-study location. Refer to NCT04333732 for list of inclusion / exclusion criteria for the study population.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Determining Biomarkers of Trained Immunity in a Randomized Controlled Trial of the Measles, Mumps, and Rubella Vaccine - a Sub-study of the CROWN CORONATION Trial
This is a substudy of NCT04333732. The goal of this sub-study is to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially viral associated products, in the MMR vaccinated compared placebo groups.
All participants are randomly assigned to MMR or placebo injection at baseline, followed by SARS-CoV-2 specific vaccination. Blood is drawn around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection.
Read the detailed description
A sub-study of the CROWN CORONATION Trial (COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION; NCT04333732). The goal of this sub-study is to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially virally associated products, in those exposed to MMR vaccine injection compared to those exposed to 0.9% sodium chloride ('normal saline') placebo injection.
A secondary objective is comparison of SARS-CoV-2 neutralization assays between MMR and placebo comparison groups around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection.
All participants are randomly assigned to MMR or placebo injection at baseline, followed by SARS-CoV-2 specific vaccination. Blood is drawn around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection. Peripheral blood mononuclear cells (PMBC) will be isolated from samples and stimulated with heterologous products (for example; Roswell Park Memorial Institute medium [RPMI; negative control], MMR [the vaccine itself as specific stimulus], severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2; heat inactivated], influenza virus [heat inactivated], toll-like receptor 3 ligand [TLR3 ligand; poly I:C], toll-like receptor 7/8 ligand [TLR7/8 ligand; R848], toll-like receptor 4 ligand [TLR4 ligand; lipopolysaccharide (LPS)]). Supernatants will be assayed by multiplex luminex protein assay at 24 hr (for example; type I interferons [IFN], interleukin [IL]-1β , IL-6, tumor necrosis factor [TNF]-α) and after 5 days (for example; IFN-γ, IL-17, IL-22, IL-10). This process of testing stimulus-response will be conducted on both the baseline and day 30 samples, collected from both the MMR and Placebo groups.
Neutralization assay will be conducted on all samples using wild-type SARS-CoV-2.
Measles IgG titres will be measured on all samples. Measles IgG titres will be used for sensitivity analysis.
- Conditions
- Covid19
- Being tested
- Heterologous stimuli, Neutralization assay
- Keywords
- COVID 19, Trained Immunity, Infectious Diseases
- Medical subject headings
- COVID-19, Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heterologous stimuliDiagnostic test
Also called For example; RPMI medium, MMR, SARS-CoV-2, Influenza, TLR3 ligand, TLR7/8 ligand, TLR4 ligand
In vitro exposure of peripheral blood mononuclear cells to heterologous stimuli
Neutralization assayDiagnostic test
In vitro measurement of neutralizing antibody activity to wild-type SARS-CoV-2
| Study group | Role | What they receive |
|---|---|---|
| Participants in the CROWN CORONATION trial | The CROWN CORONATION trial will randomly allocate adult participants to a single intramuscular injection of MMR vaccine or Placebo (0.9% saline). All participants in this sub-study receive SARS-CoV-2 specific vaccine subsequent to the MMR or Placebo injection. Receives: Diagnostic Test: Heterologous stimuli; Diagnostic Test: Neutralization assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokine (or chemokine) production in response to heterologous stimuli
Cytokines such as TNF-α, IL-1β and IL-6 produced by human monocytes, and IFN-γ produced by natural killer (NK)-cells, are markers of trained immunity and these (and other cytokines and chemokines) will be measured in supernatants of stimulated PBMCs from a cohort of participants in the CROWN CORONATION trial. All cytokines and chemokines are measured in picograms/milliliter.
Measured: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection
Secondary outcomes (1)
Neutralization assay
Neutralizing antibody activity to wild-type SARS-CoV-2
Measured: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2020
- Study start17 Dec 2020
- Primary completion28 Jun 2021
- Study completion28 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Avidan, Washington University School of Medicine
- Investigators
- Michael S Avidan, MD, Principal investigator, Washington Univeristy School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04646239
- Sponsor's protocol ID
- 202011081
- Status last verified
- Nov 2021
- First submitted
- 20 Nov 2020
- Last updated
- 26 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The project team will make the de-identified data available to the public within 1 year after publication using a public repository. Prior to that time, data will be deposited in the Washington University Open Scholarship repository. Any request for data not deposited in the repository must be directed to the Principal Investigator
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determining Biomarkers of Trained Immunity in a Randomized Controlled Trial of the Measles, Mumps, and Rubella Vaccine - a Sub-study of the CROWN CORONATION Trial
- ClinicalTrials.gov ID
- NCT04646239
- Acronym / sponsor ID
- 202011081
- Conditions
- Covid19
- Keywords
- COVID 19, Trained Immunity, Infectious Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 17 Dec 2020 (actual)
- Primary completion
- 28 Jun 2021 (actual)
- Study completion
- 28 Jun 2021 (actual)
- First posted
- 27 Nov 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.
This is a substudy of NCT04333732. The goal of this sub-study is to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially viral associated products, in the MMR vaccinated compared placebo groups.
All participants are randomly assigned to MMR or placebo injection at baseline, followed by SARS-CoV-2 specific vaccination. Blood is drawn around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection.
Detailed description
A sub-study of the CROWN CORONATION Trial (COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION; NCT04333732). The goal of this sub-study is to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially virally associated products, in those exposed to MMR vaccine injection compared to those exposed to 0.9% sodium chloride ('normal saline') placebo injection.
A secondary objective is comparison of SARS-CoV-2 neutralization assays between MMR and placebo comparison groups around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection.
All participants are randomly assigned to MMR or placebo injection at baseline, followed by SARS-CoV-2 specific vaccination. Blood is drawn around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection. Peripheral blood mononuclear cells (PMBC) will be isolated from samples and stimulated with heterologous products (for example; Roswell Park Memorial Institute medium [RPMI; negative control], MMR [the vaccine itself as specific stimulus], severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2; heat inactivated], influenza virus [heat inactivated], toll-like receptor 3 ligand [TLR3 ligand; poly I:C], toll-like receptor 7/8 ligand [TLR7/8 ligand; R848], toll-like receptor 4 ligand [TLR4 ligand; lipopolysaccharide (LPS)]). Supernatants will be assayed by multiplex luminex protein assay at 24 hr (for example; type I interferons [IFN], interleukin [IL]-1β , IL-6, tumor necrosis factor [TNF]-α) and after 5 days (for example; IFN-γ, IL-17, IL-22, IL-10). This process of testing stimulus-response will be conducted on both the baseline and day 30 samples, collected from both the MMR and Placebo groups.
Neutralization assay will be conducted on all samples using wild-type SARS-CoV-2.
Measles IgG titres will be measured on all samples. Measles IgG titres will be used for sensitivity analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants in the CROWN CORONATION trial | – | Diagnostic Test: Heterologous stimuli, Diagnostic Test: Neutralization assayThe CROWN CORONATION trial will randomly allocate adult participants to a single intramuscular injection of MMR vaccine or Placebo (0.9% saline). All participants in this sub-study receive SARS-CoV-2 specific vaccine subsequent to the MMR or Placebo injection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The CROWN CORONATION trial enrolls adults at risk of developing COVID-19 due to their work in the healthcare environment. To be eligible, prospective participants for the CROWN CORONATION trial must not have a contra-indication to receiving the live attenuated Measles, Mumps and Rubella vaccine (MMR) and must not be exposed to agents that may complicate the interpretation of findings regarding the hypothesized protective effect of MMR for the prevention of COVID-19. The sub-study will consecutively approach all participants enrolled in the CROWN CORONATION trial to elicit enrolment in the sub-study cohort.
Key inclusion criteria (1 listed)
- Prospective participant must already be enrolled into the CROWN CORONATION trial at the sub-study location. Refer to NCT04333732 for list of inclusion / exclusion criteria for the study population.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Heterologous stimuliAlso: For example; RPMI medium, MMR, SARS-CoV-2, Influenza, TLR3 ligand, TLR7/8 ligand, TLR4 ligandIn vitro exposure of peripheral blood mononuclear cells to heterologous stimuli | Diagnostic test | Participants in the CROWN CORONATION trial |
| Neutralization assayIn vitro measurement of neutralizing antibody activity to wild-type SARS-CoV-2 | Diagnostic test | Participants in the CROWN CORONATION trial |
Primary outcome
Cytokine (or chemokine) production in response to heterologous stimuli
Time frame: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection
Cytokines such as TNF-α, IL-1β and IL-6 produced by human monocytes, and IFN-γ produced by natural killer (NK)-cells, are markers of trained immunity and these (and other cytokines and chemokines) will be measured in supernatants of stimulated PBMCs from a cohort of participants in the CROWN CORONATION trial. All cytokines and chemokines are measured in picograms/milliliter.
1 secondary outcome
Neutralization assay
Time frame: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection
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 26 Nov 2021.
- Individual participant dataSharing planned: Yes. The project team will make the de-identified data available to the public within 1 year after publication using a public repository. Prior to that time, data will be deposited in the Washington University Open Scholarship repository. Any request for data not deposited in the repository must be directed to the Principal Investigator
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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.
Michael S Avidan, MD principal investigator
Washington Univeristy School of Medicine
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 Covid19, run by Washington University School of Medicine at 1 site in United States.
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 0 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 26 Nov 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 United States. 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?
Cytokine (or chemokine) production in response to heterologous stimuli (time frame: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection). 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 26 Nov 2021.