Anti-Androgen Treatment for COVID-19
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|ClinicalTrials.gov Identifier: NCT04446429|
Recruitment Status : Recruiting
First Posted : June 24, 2020
Last Update Posted : July 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19 SARS-CoV2 Androgenetic Alopecia Prostate Cancer Benign Prostatic Hyperplasia SARS (Severe Acute Respiratory Syndrome)||Drug: Dutasteride Drug: Ivermectin Drug: Azithromycin Drug: Proxalutamide||Not Applicable|
During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have reported a significant difference in the rate of severe cases between adult females and adult males (42% vs 58%).Among children under the age of 14, the rate of severe cases was reported to be extremely low. To explain this difference, several theories have been proposed including cigarette smoking and lifestyle habits. However, no theory fits both the gender difference in severe cases as well as reduced risk in pre-pubescent children. Our past research on male androgenetic alopecia (AGA) has led us to investigate an association between androgens and COVID-19 pathogenesis. In normal subjects, androgen expression demonstrates significant variation between men and women as well as between adults and pre-pubescent children.
SARS-CoV-2 primarily infects type II pneumocytes in the human lung. SARS-CoV-2 enters pneumocytes, by anchoring to the ACE2 cell surface receptor. Prior to receptor binding, viral spike proteins undergo proteolytic priming by the transmembrane protease, serine 2 (TMPRSS2). TMPRSS2 inhibition or knock down reduces ability of SARS-CoV-1 (a related virus to SARS-CoV-2) to infect cells in vitro. Additionally, TMPRSS2 also facilitates entry of influenza A and influenza B into primary human airway cells and type II pneumocytes.
The human TMPRSS2 gene has a 15 bp androgen response element and in humans, androgens are the only known transcription promoters for the TMPRSS2 gene. In a study of androgen-stimulated prostate cancer cells (LNCaP), TMPRSS2 mRNA expression increase was mediated by the androgen receptor. Further, the ACE2 receptor, also critical for SARS-CoV-2 viral infectivity, is affected by male sex hormones with higher activity found in males.
Androgenetic alopecia (AGA), often referred to as male pattern hair loss, is the most common form of hair loss among men. The development of androgenetic alopecia is androgen mediated and is dependent on genetic variants found in the androgen receptor gene located on the X chromosome; thus, it is hypothesized that men with AGA would be more prone to severe COVID-19 disease. The investigators conducted a preliminary observational study of hospitalized COVID-19 patients at two Spanish tertiary hospitals between March 23-April 6, 2020 to test this theory. In total, 41 Caucasian males admitted to the hospitals with a diagnosis of bilateral SARS-CoV-2 pneumonia were analyzed. The mean age of patients was 58 years (range 23-79). Among them, 29 (71%) were diagnosed with AGA (16 (39%) were classified as severe AGA (Hamilton IV or above)) and 12 (29%) did not present clinical signs of AGA. The diagnosis of AGA was performed clinically by a dermatologist. The precise prevalence of AGA among otherwise healthy Spanish Caucasian males is unknown; however, based on published literature, the expected prevalence of a similar age-matched Caucasian population is approximately 31-53%.
Based on the scientific rationale combined with this preliminary observation, the investigators propose to test an anti-androgen as a treatment for patients recently diagnosed with COVID-19. This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection. Provided anti-androgens are effective in reducing the rate of COVID-19 hospitalization, subjects enrolled in this study may experience a lower rate of hospitalization.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||381 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Anti-Androgen Treatment for COVID-19|
|Actual Study Start Date :||July 2, 2020|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||January 31, 2021|
Experimental: Dutasteride + Standard Care
Ivermectin+ Azythromycin + Dutasteride
0.5 mg q.d.
200 mcg/kg q.d
500 mg q.d.
Active Comparator: Standard Care
Ivermectin + Azythromycin
200 mcg/kg q.d
500 mg q.d.
Experimental: Proxalutamide + Standard Care
Ivermectin+ Azythromycin + Proxalutamide
200 mcg/kg q.d
500 mg q.d.
200 mg q.d.
- COVID-19 hospitalization [ Time Frame: 30 days ]Percentage of subjects hospitalized due to COVID-19
- COVID-19 Ordinal Outcomes Scale [ Time Frame: 30 days ]
COVID Ordinal Scale defined as:
- Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation)
- Hospitalized on non-invasive ventilation or high flow nasal cannula
- Hospitalized on supplemental oxygen
- Hospitalized not on supplemental oxygen
- Not hospitalized with limitation in activity (continued symptoms)
- Not hospitalized without limitation in activity (no symptoms)
- Symptoms severity of COVID-19 [ Time Frame: 30 days ]Symptoms severity of COVID-19 using Brescia-COVID Respiratory Severity Scale (BCRSS)/Algorithm
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04446429
|Contact: Flavio A Cadegiani, MDemail@example.com|
|Contact: Andy Goren, MDfirstname.lastname@example.org|
|Brasilia, Brazil, 70390-150|
|Contact: Flavio A Cadegiani, MD +5561996506111 email@example.com|
|Principal Investigator: Flavio A Cadegiani, MD|
|Sub-Investigator: Carlos Wambier, MD|
|Principal Investigator:||Flavio A Cadegiani, MD||Corpometria Institute|
|Study Director:||Andy Goren, MD||Applied Biology, Inc.|