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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04368897
Recruitment Status : Recruiting
First Posted : April 30, 2020
Last Update Posted : July 14, 2020
Sponsor:
Collaborator:
Hospital Universitario Ramon y Cajal
Information provided by (Responsible Party):
Applied Biology, Inc.

Tracking Information
First Submitted Date April 27, 2020
First Posted Date April 30, 2020
Last Update Posted Date July 14, 2020
Actual Study Start Date May 1, 2020
Estimated Primary Completion Date September 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 28, 2020)
  • Hospital-free days to Day 28 [ Time Frame: 28 days] [ Time Frame: 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.
  • 1. Severity of Disease [ Time Frame: Day 28 ]
    Defined as discharged, hospitalization, admission to intensive care unit [ICU] and death
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title In-vitro Diagnostic Test to Predict COVID-19 Mortality and Disease Severity
Official Title In-vitro Diagnostic Test to Predict COVID-19 Mortality and Disease Severity
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.
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 Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Saliva DNA sample
Sampling Method Non-Probability Sample
Study Population Patients admitted to the hospital due to COVID-19
Condition
  • SARS-CoV 2
  • COVID
  • COVID-19
  • Androgenetic Alopecia
  • Androgen Receptor Abnormal
  • Androgen Deficiency
Intervention
  • Diagnostic Test: CAG length <22
    CAG repeat length in exon 1 of AR gene
    Other Name: Genetic Test - Short CAG Allele
  • Diagnostic Test: CAG length >=22
    CAG repeat length in exon 1 of AR gene
    Other Name: Genetic Test - Long CAG Allele
Study Groups/Cohorts COVID-19 Male Patients
Males with laboratory confirmed SARS-CoV-2 infection
Interventions:
  • Diagnostic Test: CAG length <22
  • Diagnostic Test: CAG length >=22
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 28, 2020)
200
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 1, 2020
Estimated Primary Completion Date September 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Self description
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Sabina Herrera, MD 9493874526 sabinapi@hotmail.com
Contact: Andy Goren, MD andyg@appliedbiology.com
Listed Location Countries Spain
Removed Location Countries  
 
Administrative Information
NCT Number NCT04368897
Other Study ID Numbers AB-IVD-CoV-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Applied Biology, Inc.
Study Sponsor Applied Biology, Inc.
Collaborators Hospital Universitario Ramon y Cajal
Investigators
Principal Investigator: Sabina Herrera, MD Hospital Universitario Ramon y Cajal
Study Director: Carlos Wambier, MD Brown University
PRS Account Applied Biology, Inc.
Verification Date July 2020