Anti-Androgen Treatment for COVID-19
关键词
抽象
描述
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.
日期
最后验证: | 06/30/2020 |
首次提交: | 06/21/2020 |
提交的预估入学人数: | 06/22/2020 |
首次发布: | 06/23/2020 |
上次提交的更新: | 07/27/2020 |
最近更新发布: | 07/28/2020 |
实际学习开始日期: | 07/01/2020 |
预计主要完成日期: | 12/30/2020 |
预计完成日期: | 01/30/2021 |
状况或疾病
干预/治疗
Drug: Dutasteride + Standard Care
Drug: Ivermectin
Drug: Azithromycin
Drug: Proxalutamide + Standard Care
相
手臂组
臂 | 干预/治疗 |
---|---|
Experimental: Dutasteride + Standard Care Ivermectin+ Azythromycin + Dutasteride | Drug: Dutasteride + Standard Care 0.5 mg q.d. |
Active Comparator: Standard Care Ivermectin + Azythromycin | |
Experimental: Proxalutamide + Standard Care Ivermectin+ Azythromycin + Proxalutamide | Drug: Proxalutamide + Standard Care 200 mg q.d. |
资格标准
有资格学习的年龄 | 50 Years 至 50 Years |
有资格学习的性别 | Male |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: 1. Male 2. Age ≥50 years old 3. Presenting "Gabrin sign" i.e., androgenetic alopecia (Norwood-Hamilton grade ≥ III) 4. Positive SARS-CoV-2 rtPCR test in the past 7 days 5. Not hospitalized for acute respiratory symptoms 6. Willing to provide informed consent Exclusion Criteria: 1. Subject enrolled in a study to investigate a COVID-19 drug 2. Subject taking an anti-androgen 3. Hypothyroidism 4. Not willing to provide informed consent |
结果
主要结果指标
1. COVID-19 hospitalization [30 days]
2. COVID-19 Ordinal Outcomes Scale [30 days]
次要成果指标
1. Symptoms severity of COVID-19 [30 days]