In-vitro Diagnostic Test to Predict COVID-19 Mortality and Disease Severity

Sponsor
Applied Biology, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04368897
Collaborator
Hospital Universitario Ramon y Cajal (Other)
200
Enrollment
1
Location
31
Anticipated Duration (Months)
6.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The COVID-19 Androgen Sensitivity Test is a non-invasive In-Vitro Diagnostic device that utilizes Next Generation Sequencing Technology (NGS). The results of the test are used by a physician to assess the risk of developing severe symptoms following COVID-19 infection, The COVID-19 Androgen Sensitivity Test requires a health care professional to collect a DNA sample using an FDA cleared DNA sample collection kit.

Condition or DiseaseIntervention/TreatmentPhase
  • Diagnostic Test: CAG length <22
  • Diagnostic Test: CAG length >=22

Detailed Description

In late 2019, a novel coronavirus, subsequently named SARS-CoV-2 (COVID-19), was first reported in Hubei province in China. Since it was first reported, a worldwide pandemic has ensued affecting more than 450,000 individuals as of March 2020. In the midst of the pandemic, epidemiological reports unveiled a disproportionate low rate of severe cases among adult females compared to adult males, 42% and 58%, respectively. Similarly, the rate of severe cases among pre-pubescent children was exceptionally low at 0.6%. An explanation for the skewed prevalence of severe COVID-19 infection in adult males has yet to be elucidated.

In newborns, it has long been recognized that male infants are more susceptible to respiratory distress syndrome and less likely to respond to prenatal glucocorticoid therapy to protect against respiratory distress. Respiratory distress is intimately tied to the production of pulmonary surfactant, e.g., pulmonary surfactant proteins have been demonstrated to protect against influenza A. In animal studies, it was demonstrated that a sexual dimorphism in fetal pulmonary surfactant production is influenced by the androgen receptor (AR). For example, in rabbits, dihydrotestosterone was shown to inhibit fetal pulmonary surfactant production in both males and females while an anti-androgen, flutamide, was demonstrated to remove the sexual dimorphism in surfactant production. While severe COVID-19 symptoms are primarily manifested in older adults, the similar sexual dimorphism in the severity of respiratory disease is of interest. In addition, AR expression is low prior to pubertal maturation and may contribute to the low incidence of severe COVID-19 infection in children. As such, the investigators propose that the lower rate of severe COVID-19 infection in female patients may be attributed to lower androgen receptor expression.

Additional evidence to the possible implication of androgens in COVID-19 infection severity is found in the molecular mechanism required for SARS-CoV-2 infectivity. SARS-CoV-2 is part of the coronavirus family of viruses including SARS-CoV-1 and MERS-CoV. Coronavirus predominantly infects type II pneumocytes in the human lung. Previously, it was demonstrated that SARS-CoV-2 cell entry depends on priming of a viral spike surface protein by transmembrane protease serine 2 (TMPRSS2) present in the host. In type II pneumocytes, TMPRSS2 expression is associated with an increase in androgen receptor (AR) expression, specifically connecting AR expression to SARS-CoV-2, due to AR-regulated TMPRSS2 gene promoter. Moreover, angiotensin converting enzyme 2 (ACE2) has been recognized as the attachment molecule to the viral spike surface protein, thus termed the "receptor of SARS-CoV-2". Interestingly, ACE2 has been shown to have reduced activity by the decrease of androgen hormones (experimental orchidectomy), possibly by decreased expression of ACE2.

A well known polymorphism of the androgen receptor is a CAG repeat in the first exon of AR gene. The number of CAG repeats has been correlated with AR function and expression. The primary purpose of this study is to evaluate the association of AR gene polymorphisms with disease severity and mortality following COVID-19 infection. If an association can be elucidated, it would imply novel treatment modalities. For example, the activation of AR can be reduced by several classes of drugs including androgen receptor antagonists, androgen synthesis inhibitors and antigonadotropins.

Study Design

Study Type:
Observational
Anticipated Enrollment :
200 participants
Observational Model:
Case-Control
Time Perspective:
Prospective
Official Title:
In-vitro Diagnostic Test to Predict COVID-19 Mortality and Disease Severity
Actual Study Start Date :
May 1, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

ArmIntervention/Treatment
COVID-19 Male Patients

Males with laboratory confirmed SARS-CoV-2 infection

Diagnostic Test: CAG length <22
CAG repeat length in exon 1 of AR gene
Other Names:
  • Genetic Test - Short CAG Allele
  • Diagnostic Test: CAG length >=22
    CAG repeat length in exon 1 of AR gene
    Other Names:
  • Genetic Test - Long CAG Allele
  • Outcome Measures

    Primary Outcome Measures

    1. Hospital-free days to Day 28 [ Time Frame: 28 days] [28 days]

      Defined as 28 days minus the number of days from randomization to discharge home. If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.

    2. 1. Severity of Disease [Day 28]

      Defined as discharged, hospitalization, admission to intensive care unit [ICU] and death

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Inclusion Criteria:
    • Male over the age of 18

    • First time present at the site

    • Laboratory confirmed SARS-CoV-2 infection

    • Able to give informed consent

    Exclusion Criteria:
    • Unable to give informed consent

    • Diagnosed with an additional respiratory co-infection

    • XXY males

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Hospital Universitario Ramon y CajalMadridSpain

    Sponsors and Collaborators

    • Applied Biology, Inc.
    • Hospital Universitario Ramon y Cajal

    Investigators

    • Principal Investigator: Sabina Herrera, MD, Hospital Universitario Ramon y Cajal
    • Study Director: Carlos Wambier, MD, Brown University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Applied Biology, Inc.
    ClinicalTrials.gov Identifier:
    NCT04368897
    Other Study ID Numbers:
    • AB-IVD-CoV-001
    First Posted:
    Apr 30, 2020
    Last Update Posted:
    Feb 18, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 18, 2022