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

July 18, 2023 updated by: Applied Biology, Inc.
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Madrid, Spain
        • Hospital Universitario Ramón y Cajal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Patients admitted to the hospital due to COVID-19

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
28 days
1. Severity of Disease
Time Frame: Day 28
Defined as discharged, hospitalization, admission to intensive care unit [ICU] and death
Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Applied Biology, Inc.

Collaborators

Hospital Universitario Ramon y Cajal

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2020

Primary Completion (Actual)

December 1, 2022

Study Completion (Actual)

December 1, 2022

Study Registration Dates

First Submitted

April 27, 2020

First Submitted That Met QC Criteria

April 28, 2020

First Posted (Actual)

April 30, 2020

Study Record Updates

Last Update Posted (Actual)

July 19, 2023

Last Update Submitted That Met QC Criteria

July 18, 2023

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AB-IVD-CoV-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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