Ignite Creation Date:
2024-05-06 @ 2:35 PM
Last Modification Date:
2024-10-26 @ 1:33 PM
Study NCT ID:
NCT04361422
Status:
UNKNOWN
Last Update Posted:
2020-09-23
First Post:
2020-04-21
Brief Title:
Isotretinoin in Treatment of COVID-19
Sponsor:
Tanta University
Organization:
Tanta University
Study Overview
Official Title:
Evaluation of the Safety and Efficacy of Isotretinoin in Treatment of COVID-19 Clinical Study
Status:
UNKNOWN
Status Verified Date:
2020-09
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Randomized
Brief Summary:
Contributors
Lamia Elgarhy Sabah El-Gaeish 1 Eman Hamed 2 Wagdy Fathy2 Department of Dermatology Department of Pharmacology1 Faculty of Medicine Tanta University Department of Chest Faculty of Medicine Suez Canal University2
Abstract
The COVID-19 pandemic caused by SARS-COV-2 has infected over 2000000 people causing over 150000 deaths A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 ACE2 whose expression has been demonstrated in many tissues including alveolar epithelial type II cells in lungs oral mucosa and intestine heart kidney endothelium and skin ACE2-expressing cells can act as home cells and are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication 1 Fang et al has suggested that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection as these patients are often treated with ACE inhibitors ACEIs or angiotensin II type-I receptor blockers ARBs which have been previously suggested to increase ACE2 expression 2 In another study by Sinha et al who analyzed a publicly available Connectivity Map CMAP dataset of prepost transcriptomic profiles for drug treatment in cell lines for over 20000 small molecules isotretinoin was the strongest down-regulator of ACE 2 receptors On the other hand they found 6 drugs in CMAP that are currently being investigated in clinical trials for treating COVID-19 chloroquine thalidomide methylprednisolone losartan lopinavir and ritonavir from clinicaltrialsgov none of which was found to significantly alter ACE2 expression P01 3 Moreover Wu et al demonstrated that isotretinoin is a Potential papain like protease PLpro inhibitors which is a protein encoded by SARS-CoV-2 genes and considered one of the proteins that should be targeted in COVID-19 treatment by performing target-based virtual ligand screening 4 In addition isotretinoin was reported to increase CD4 counts and markedly decrease viremia in HIV positive patients suffering from acne vulgaris 5 Currently a study is running to evaluate the effect of isotretinoin on immune activation among HIV-1 infected subjects with incomplete CD4 T cell recovery 6 From this point we can suggest that patient taking isotretinoin therapy may be immune against SARS-COV-2 and it can also have a therapeutic effect by prevention of further progression of the virus Several potential mechanisms of action of ChloroquineHydroxychloroquine against SARS-CoV-2 have been postulated and they are actually used in treatment regimens for COVID-197 It was reported that chloroquine increase the blood level of isotretinoin so lower doses is required when combined We assume to test the efficacy of isotretinoin in treatment of COVID-19 versus combined therapy with the standard treatment of COVID-19
Lamia Elgarhy Sabah El-Gaeish 1 Eman Hamed 2 Wagdy Fathy2 Department of Dermatology Department of Pharmacology1 Faculty of Medicine Tanta University Department of Chest Faculty of Medicine Suez Canal University2
Abstract
The COVID-19 pandemic caused by SARS-COV-2 has infected over 2000000 people causing over 150000 deaths A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 ACE2 whose expression has been demonstrated in many tissues including alveolar epithelial type II cells in lungs oral mucosa and intestine heart kidney endothelium and skin ACE2-expressing cells can act as home cells and are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication 1 Fang et al has suggested that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection as these patients are often treated with ACE inhibitors ACEIs or angiotensin II type-I receptor blockers ARBs which have been previously suggested to increase ACE2 expression 2 In another study by Sinha et al who analyzed a publicly available Connectivity Map CMAP dataset of prepost transcriptomic profiles for drug treatment in cell lines for over 20000 small molecules isotretinoin was the strongest down-regulator of ACE 2 receptors On the other hand they found 6 drugs in CMAP that are currently being investigated in clinical trials for treating COVID-19 chloroquine thalidomide methylprednisolone losartan lopinavir and ritonavir from clinicaltrialsgov none of which was found to significantly alter ACE2 expression P01 3 Moreover Wu et al demonstrated that isotretinoin is a Potential papain like protease PLpro inhibitors which is a protein encoded by SARS-CoV-2 genes and considered one of the proteins that should be targeted in COVID-19 treatment by performing target-based virtual ligand screening 4 In addition isotretinoin was reported to increase CD4 counts and markedly decrease viremia in HIV positive patients suffering from acne vulgaris 5 Currently a study is running to evaluate the effect of isotretinoin on immune activation among HIV-1 infected subjects with incomplete CD4 T cell recovery 6 From this point we can suggest that patient taking isotretinoin therapy may be immune against SARS-COV-2 and it can also have a therapeutic effect by prevention of further progression of the virus Several potential mechanisms of action of ChloroquineHydroxychloroquine against SARS-CoV-2 have been postulated and they are actually used in treatment regimens for COVID-197 It was reported that chloroquine increase the blood level of isotretinoin so lower doses is required when combined We assume to test the efficacy of isotretinoin in treatment of COVID-19 versus combined therapy with the standard treatment of COVID-19
Detailed Description:
The study is a randomized interventional comparative Phase III trial The duration of the trial for each subject is expected to be 3 months The duration for each individual subject includes one-month study treatment and 3 months follow-up time Recruitment of subjects will start in April 2020
150 adult male and female patients with positive COVID-19 diagnosis and fulfilling the below outlined inclusion criteria will be enrolled into the study Trial population will consist of both genders
Name of tested drug Isotretinoin All consenting adult patients having confirmed COVID-19 will be recruited and randomly and blindly allocated in a 111 ratio to the following arms
Group 1 50 patients will receive isotretinoin 05 mgkgday for one month or until viral clearance
Group 2 50 patients will receive standard therapy for COVID-19 Paracetamol 500 mg 6h Hydroxychloroquine 500 mg 12h Oseltamivir 150 mg 12 h for 5 days Azithromycin 1 gm first day then 500 mgday for 1st line or Clarithromycin 500 mg12 h for 7-14 days Ascorbic acid 500 mg12 h and Cyanocobalamin IV once daily plus Lopinavir 400mgRitonavir 100 mg caps 2 capsules twice daily in severe cases
Group 3 50 patients will receive standard therapy for COVID-19 isotretinoin 025 mgkgday for one month or until viral clearance
Inclusion Criteria
Clinical and laboratory diagnosis of COVID-19
Age range 18-40
Exclusion Criteria
Have the following conditions
1 Hypercholesterolemia
2 Hypertriglyceridemia
3 Liver disease
4 Renal disease
5 Sjögren syndrome
6 Pregnancy
7 Lactation
8 Depressive disorder
9 Contraindications for hormonal contraception or intrauterine device
150 adult male and female patients with positive COVID-19 diagnosis and fulfilling the below outlined inclusion criteria will be enrolled into the study Trial population will consist of both genders
Name of tested drug Isotretinoin All consenting adult patients having confirmed COVID-19 will be recruited and randomly and blindly allocated in a 111 ratio to the following arms
Group 1 50 patients will receive isotretinoin 05 mgkgday for one month or until viral clearance
Group 2 50 patients will receive standard therapy for COVID-19 Paracetamol 500 mg 6h Hydroxychloroquine 500 mg 12h Oseltamivir 150 mg 12 h for 5 days Azithromycin 1 gm first day then 500 mgday for 1st line or Clarithromycin 500 mg12 h for 7-14 days Ascorbic acid 500 mg12 h and Cyanocobalamin IV once daily plus Lopinavir 400mgRitonavir 100 mg caps 2 capsules twice daily in severe cases
Group 3 50 patients will receive standard therapy for COVID-19 isotretinoin 025 mgkgday for one month or until viral clearance
Inclusion Criteria
Clinical and laboratory diagnosis of COVID-19
Age range 18-40
Exclusion Criteria
Have the following conditions
1 Hypercholesterolemia
2 Hypertriglyceridemia
3 Liver disease
4 Renal disease
5 Sjögren syndrome
6 Pregnancy
7 Lactation
8 Depressive disorder
9 Contraindications for hormonal contraception or intrauterine device
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None