COVID-19NCT04394884
Pathogenesis of BTK-mediated Hyper-Inflammatory Responses in COVID-19 (RESPOND)
An observational study of COVID-19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial summary
Background: Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome. It is caused by the SARS-CoV-2 virus. People with severe COVID-19 infection have a hyper-inflammatory response. Bruton tyrosine kinase (BTK) plays a role in the innate immune system. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- How many people
- 0 participants
- Where
- 3 sitesUnited States
- Study dates
- 17 Feb 2022to 17 Feb 2022
- 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
- No healthy volunteers
- Adult, Older adult
Study population: people admitted to the participating sites who have COVID-19 or some other disease were they are already receiving or will receive BTK therapy
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Ability to provide informed consent, and
- Men and women >=18 years of age at the time of signing the informed consent form, and
- Diagnosis of COVID-19 in hospitalized patients with hypoxemia (SpO2 less than or equal to 94% on room air), with plan to receive or not receive BTK inhibition for clinical or for external research study purposes, or
- Does not have COVID-19 and does have plan to receive BTK inhibition therapy for a clinical indication other than COVID-19 (either hospitalized or not).
Who cannot join
- Individuals meeting any of the following criteria will be excluded from study participation:
- Documented history of hemoglobin from most recent blood draw <7g/dL if known.
- Pregnant or breastfeeding.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Johns Hopkins Hospital
Baltimore, Maryland, 21205
Walter Reed National Medical Center
Bethesda, Maryland, 20301
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Pathogenesis of BTK-mediated Hyper-Inflammatory Responses in COVID-19
Background:
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome. It is caused by the SARS-CoV-2 virus. People with severe COVID-19 infection have a hyper-inflammatory response. Bruton tyrosine kinase (BTK) plays a role in the innate immune system. BTK inhibition can be used to target the innate immune system that appears to contribute to mortality. This could be an effective way to help the inflammatory responses in people with COVID-19.
Read more
Objective:
To learn more about the immunologic mechanisms by which BTK inhibition may decrease hyper-inflammatory responses in people with COVID-19.
Eligibility:
People ages 18 and older in one of the following groups:
- They are in the hospital with COVID-19. They will or will not be treated with a BTK inhibitor.
- They do not have COVID-19. They are or are not in the hospital. They will be treated with a BTK inhibitor for a reason other than COVID-19.
Design:
Participants will be screened with a review of their demographic and clinical information. Their medical history will be reviewed. If they have COVID-19, their symptoms will be assessed.
Participants will give 3-4 blood samples. These may be taken through a vein. They may also be taken through an existing central venous catheter.
Participants may give a stool sample. This will be collected by nursing staff. It will be collected using a stool collection vial. Stool collection is optional.
Participants samples will be collected over about 7 days. These will be used for research and genetic testing.
Read the detailed description
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Severe COVID-19 infection is associated with a hyper-inflammatory response and evidence of innate immune cell activation. Bruton tyrosine kinase (BTK) plays a central role in innate immune cell signaling and activation and BTK inhibition represents a promising therapeutic strategy for ameliorating excessive inflammatory responses in patients with COVID-19. Understanding the mechanisms by which BTK inhibition modulates the host inflammatory response in patients with COVID-19 is critical in order to better understand COVID-19 pathogenesis.
In this multisite natural history laboratory study, hospitalized patients with COVID-19 (n=80) will be recruited at Walter Reed National Military Medical Center and The Johns Hopkins Hospital. Forty of these patients will be recipients of BTK inhibition, either as part of their standard clinical care or in another clinical trial. The other 40 will not be recipients of BTK inhibition and will serve as a control group. A third group of patients without COVID-19 (n=40) who will be recipients of BTK inhibition for other clinical indications will also be enrolled as a second control group.
Participants will have three or four longitudinal blood draws and may be asked to provide stool samples. All specimens and data will be coded and sent to the National Institutes of Health (NIH) for research analysis. Only site investigators will have access to the code s key for their respective sites; the NIH investigators will not have the keys. Coded blood samples will be used for genetic testing, transcriptional analyses, deep immunological phenotyping, soluble biomarker analysis, and other research tests. Coded clinical and laboratory data from routine care (e.g., basic demographic information, vital signs, medications, clinical labs, and radiologic imaging findings) will also be captured. Coded stool samples may be collected as part of this study to determine whether viable SARS-CoV-2 is present in stool, which will help advance our understanding of pathogenesis and enteric transmission.
- Conditions
- COVID-19
- Keywords
- Sample Collection, Immunological Mechanisms, SARS-CoV-2, Serelogic Response, Imflammatory Pathway
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| COVID-19 - | will receive BTK therapy for other reasons | |
| COVID-19 + BTK | will receive BTK therapy | |
| COVID-19 + No BTK | will not receive BTK therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize the immunologic mechanisms by which BTK inhibition may ameliorate hyper- inflammatory responses in patients with COVID-19.
Inflammatory pathway analyses following BTK inhibition in COVID-19 patients.
Measured: day 0, 1,3,7
Secondary outcomes (7)
1. Characterization of TLR3 and TLR7/8-dependent immunologic phenotypes in COVID-19 patients before and after BTK inhibition.
Transcriptomic, genomic, serological and immunologic analyses of response to BTK inhibition therapy in COVID- 19 patients.
Measured: day 0, 1,3,7
2. Evaluation of mechanisms of immune cell-specific activation, cytokine production, exhaustion and apoptosis in COVID-19 patients before and after BTK inhibition.
Transcriptomic, genomic, serological and immunologic analyses of response to BTK inhibition therapy in COVID- 19 patients.
Measured: day 0, 1,3,7
3. Transcriptional, chromatin, and epigenetic profiling of immune cells at the single cell level in COVID-19 patients before and after BTK inhibition.
Transcriptomic, genomic, serological and immunologic analyses of response to BTK inhibition therapy in COVID- 19 patients.
Measured: day 0, 1,3,7
4. Longitudinal evaluation of TCR and BCR repertoire development in COVID-19 patients before and after BTK inhibition.
Transcriptomic, genomic, serological and immunologic analyses of response to BTK inhibition therapy in COVID- 19 patients.
Measured: day 0, 1,3,7
5. Characterization of SARS- CoV-2 serological responses in COVID-19 patients with and without BTK inhibition.
Transcriptomic, genomic, serological and immunologic analyses of response to BTK inhibition therapy in COVID- 19 patients.
Measured: day 0, 1,3,7
6. Characterization of genetic variants that correlate with disease severity and/or response to BTK inhibition treatment.
Transcriptomic, genomic, serological and immunologic analyses of response to BTK inhibition therapy in COVID- 19 patients.
Measured: day 0, 1,3,7
7. Evaluation of soluble biomarkers as surrogate markers of hyper- inflammation/prognosis and of response to BTK inhibition therapy in COVID-19 patients
Transcriptomic, genomic, serological and immunologic analyses of response to BTK inhibition therapy in COVID- 19 patients.
Measured: day 0, 1,3,7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2020
- Study start17 Feb 2022
- Primary completion17 Feb 2022
- Study completion17 Feb 2022
Why it stopped: Study never started, no subjects enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michail S Lionakis, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04394884
- Sponsor's protocol ID
- 200114
- Other IDs
- 20-I-0114
- Status last verified
- Feb 2022
- First submitted
- 19 May 2020
- Last updated
- 24 Feb 2022
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathogenesis of BTK-mediated Hyper-Inflammatory Responses in COVID-19
- ClinicalTrials.gov ID
- NCT04394884
- Acronym / sponsor ID
- 200114
- Conditions
- COVID-19
- Keywords
- Sample Collection, Immunological Mechanisms, SARS-CoV-2, Serelogic Response, Imflammatory Pathway
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Study never started, no subjects enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 17 Feb 2022 (actual)
- Primary completion
- 17 Feb 2022 (actual)
- Study completion
- 17 Feb 2022 (actual)
- First posted
- 20 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.
Background:
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome. It is caused by the SARS-CoV-2 virus. People with severe COVID-19 infection have a hyper-inflammatory response. Bruton tyrosine kinase (BTK) plays a role in the innate immune system. BTK inhibition can be used to target the innate immune system that appears to contribute to mortality. This could be an effective way to help the inflammatory responses in people with COVID-19.
Objective:
To learn more about the immunologic mechanisms by which BTK inhibition may decrease hyper-inflammatory responses in people with COVID-19.
Eligibility:
People ages 18 and older in one of the following groups:
- They are in the hospital with COVID-19. They will or will not be treated with a BTK inhibitor.
- They do not have COVID-19. They are or are not in the hospital. They will be treated with a BTK inhibitor for a reason other than COVID-19.
Design:
Participants will be screened with a review of their demographic and clinical information. Their medical history will be reviewed. If they have COVID-19, their symptoms will be assessed.
Participants will give 3-4 blood samples. These may be taken through a vein. They may also be taken through an existing central venous catheter.
Participants may give a stool sample. This will be collected by nursing staff. It will be collected using a stool collection vial. Stool collection is optional.
Participants samples will be collected over about 7 days. These will be used for research and genetic testing.
Detailed description
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Severe COVID-19 infection is associated with a hyper-inflammatory response and evidence of innate immune cell activation. Bruton tyrosine kinase (BTK) plays a central role in innate immune cell signaling and activation and BTK inhibition represents a promising therapeutic strategy for ameliorating excessive inflammatory responses in patients with COVID-19. Understanding the mechanisms by which BTK inhibition modulates the host inflammatory response in patients with COVID-19 is critical in order to better understand COVID-19 pathogenesis.
In this multisite natural history laboratory study, hospitalized patients with COVID-19 (n=80) will be recruited at Walter Reed National Military Medical Center and The Johns Hopkins Hospital. Forty of these patients will be recipients of BTK inhibition, either as part of their standard clinical care or in another clinical trial. The other 40 will not be recipients of BTK inhibition and will serve as a control group. A third group of patients without COVID-19 (n=40) who will be recipients of BTK inhibition for other clinical indications will also be enrolled as a second control group.
Participants will have three or four longitudinal blood draws and may be asked to provide stool samples. All specimens and data will be coded and sent to the National Institutes of Health (NIH) for research analysis. Only site investigators will have access to the code s key for their respective sites; the NIH investigators will not have the keys. Coded blood samples will be used for genetic testing, transcriptional analyses, deep immunological phenotyping, soluble biomarker analysis, and other research tests. Coded clinical and laboratory data from routine care (e.g., basic demographic information, vital signs, medications, clinical labs, and radiologic imaging findings) will also be captured. Coded stool samples may be collected as part of this study to determine whether viable SARS-CoV-2 is present in stool, which will help advance our understanding of pathogenesis and enteric transmission.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| COVID-19 - | – | –will receive BTK therapy for other reasons |
| COVID-19 + BTK | – | –will receive BTK therapy |
| COVID-19 + No BTK | – | –will not receive BTK therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- people admitted to the participating sites who have COVID-19 or some other disease were they are already receiving or will receive BTK therapy
Key inclusion criteria (5 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Ability to provide informed consent, and
- Men and women >=18 years of age at the time of signing the informed consent form, and
- Diagnosis of COVID-19 in hospitalized patients with hypoxemia (SpO2 less than or equal to 94% on room air), with plan to receive or not receive BTK inhibition for clinical or for external research study purposes, or
- Does not have COVID-19 and does have plan to receive BTK inhibition therapy for a clinical indication other than COVID-19 (either hospitalized or not).
Key exclusion criteria (4 listed)
- Individuals meeting any of the following criteria will be excluded from study participation:
- Documented history of hemoglobin from most recent blood draw <7g/dL if known.
- Pregnant or breastfeeding.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To characterize the immunologic mechanisms by which BTK inhibition may ameliorate hyper- inflammatory responses in patients with COVID-19.
Time frame: day 0, 1,3,7
Inflammatory pathway analyses following BTK inhibition in COVID-19 patients.
7 secondary outcomes
1. Characterization of TLR3 and TLR7/8-dependent immunologic phenotypes in COVID-19 patients before and after BTK inhibition.
Time frame: day 0, 1,3,7
2. Evaluation of mechanisms of immune cell-specific activation, cytokine production, exhaustion and apoptosis in COVID-19 patients before and after BTK inhibition.
Time frame: day 0, 1,3,7
3. Transcriptional, chromatin, and epigenetic profiling of immune cells at the single cell level in COVID-19 patients before and after BTK inhibition.
Time frame: day 0, 1,3,7
4. Longitudinal evaluation of TCR and BCR repertoire development in COVID-19 patients before and after BTK inhibition.
Time frame: day 0, 1,3,7
5. Characterization of SARS- CoV-2 serological responses in COVID-19 patients with and without BTK inhibition.
Time frame: day 0, 1,3,7
6. Characterization of genetic variants that correlate with disease severity and/or response to BTK inhibition treatment.
Time frame: day 0, 1,3,7
7. Evaluation of soluble biomarkers as surrogate markers of hyper- inflammation/prognosis and of response to BTK inhibition therapy in COVID-19 patients
Time frame: day 0, 1,3,7
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2022.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Michail S Lionakis, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites 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 5 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: withdrawn, as of the sponsor's last update on 24 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 was withdrawn before enrolling participants, so there are no results.
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?
To characterize the immunologic mechanisms by which BTK inhibition may ameliorate hyper- inflammatory responses in patients with COVID-19. (time frame: day 0, 1,3,7). 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 24 Feb 2022.