Pathogenesis of BTK-mediated Hyper-Inflammatory Responses in COVID-19 (RESPOND)

NCT04394884 | Withdrawn

• 2 other identifiers: 20011420-I-0114
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

COVID-19

Keywords

Sample Collection; Immunological Mechanisms; SARS-CoV-2; Serelogic Response; Imflammatory Pathway

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  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.

  day 0, 1,3,7

• 4. Longitudinal evaluation of TCR and BCR repertoire development in COVID-19 patients before and after BTK inhibition.

  day 0, 1,3,7

• 5. Characterization of SARS- CoV-2 serological responses in COVID-19 patients with and without BTK inhibition.

  day 0, 1,3,7

Study Arms (3)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Walter Reed National Medical Center

Bethesda, Maryland, 20301, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Michail S Lionakis, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 20, 2020
• Study Start: February 17, 2022
• Primary Completion: February 17, 2022
• Study Completion: February 17, 2022
• Last Updated: February 24, 2022

Record last verified: 2022-02

Locations

US (3)