Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
Trial no.: PACTR202005599385499 Date of Approval: 11/05/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Folic acid: A new suggested prevention and treatment of COVID-19 infection.
Official scientific title The host Epigenetic methylation repair in COVID-19 using Folic acid: A new suggested prevention and treatment.
Brief summary describing the background and objectives of the trial Epigenetics had been used successfully in the treatment of Viruses such as HIV and HCMV. Folic acid is known to correct epigenetic methylation pathway (1). Folic acid had been used to correct methylation defects through epigenetic pathway in prevention of Neural tube defects such as spina bifida an is recommended by the FDA to be given as 600 micro-gram in pregnant females which prove the safety of the medication. It is also used in prevention of precancerous colonic lesions such as Polyps in addition to other therapeutic uses(2). COVID-19 damages the immune system and organs through epigenetics and methylation pathway (3). In this study we suggest the use of Folic Acid stabilizes the DNA of human beings through methylation of the chromatin reader sites of the histone through epigenetic route which is the main site of action of COVID-19. Another study from Iran suggested the use of Folic acid in prevention and treatment of COVID-19 cases and proved that it decreases the intracellular transport of the virus through a trans-membrane protein called Furin (4). This study aims at detection of role of folic acid in prevention and control of COVID-19. 1. Zeina Nehme, Sébastien Pasquereau and Georges Herbein: Control of viral infections by epigenetictargeted therapy. Nehme et al. Clinical Epigenetics (2019) 11:55 https://doi.org/10.1186/s13148-019-0654-9 2. Krista S. Crider, Thomas P. Yang, Robert J Berry, and Lynn B. Bailey: Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate’s Role. Nehme et al. Clinical Epigenetics (2019) 11:55 https://doi.org/10.1186/s13148-019-0654-9 3. https://www.whatisepigenetics.com/a-look-into-the-epigenetics-of-a-coronavirus-infection/ 4. Zahra Sheybani, Maryam Heydari Dokoohaki, Manica Negahdaripour, Mehdi Dehdashti, Hassan Zolghadr, Mohsen Moghadami, Seyed Masoom Masoompour, Amin Reza Zolghadr: The Role of Folic Acid in the Management of Respiratory Disease Ca
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Prevention
Anticipated trial start date 20/04/2020
Actual trial start date 20/04/2020
Anticipated date of last follow up 21/05/2020
Actual Last follow-up date 21/05/2020
Anticipated target sample size (number of participants) 60
Actual target sample size (number of participants) 60
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Folic acid oral tablet. 500-1000 micro gram per day as a single or divided doses. 4 weeks. 3 population: 1. Health care works at risk while caring for COVID-19 carriers and cases. This poulation include: Control group: will receive the already established protocols for prevention. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. 2. Asymptomatic carriers with positive PCR.This poulation include: Control group: will receive the already established protocols for treatment. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. 3. Non-critical symptomatic COVID-!9 cases diagnosed by PCR. This poulation include: Control group: will receive the already established protocols for treatment. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. 30
Control Group Already established protocols for prevevntion and treatment Daily one month PPE for the health care workors at risk while caring of COVID-19 cases, Hydeoxycloroquin and Zithromycin for the asynptomatic controls and non-critical cases. 30 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Health care works at risk while caring for COVID-19 carriers and cases. 2. Asymptomatic carriers with positive PCR. 3. Non-critical symptomatic COVID-!9 cases diagnosed by PCR. Critical ICU admitted critical symptomatic COVID-!9 cases diagnosed by PCR. COVID-!9 cases diagnosed by PCR 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 16/04/2020 Faculty of Medicine. Cairo university
Ethics Committee Address
Street address City Postal code Country
Manial street Cairo 35855 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome a. The conversion of health care workers at risk of COVID-19 from negative to positive as measured by PCR in the control and intervention groups. b. The conversion from positive to negative in asymptomatic carriers and non-critical symptomatic COVID-19 patients in the control and intervention groups. 1 and 30 days
Secondary Outcome Rate and number of cases converted from PCR positive to PCR negative and the time needed for such conversion in the experimental as compared to the control group among the populations of Asymptomatic carriers and non-critical cases .and percentage lost from the health care providers due to their infection with COVID-19 virus. 1,2 and 4 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kasr Alainy University Hospital. Manial street. Cairo Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Faculty of Medicine Cairo university Manail street. Cairo 35855 Egypt University
COLLABORATORS
Name Street address City Postal code Country
Nadia Hafez Ouda Department of Microbiology. Faculty of Medicine. Cairo University, Almanial street 1 Cairo 35855 Egypt
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ahmed Farag farag2a@gmail.com +201001406432 Manial Street
City Postal code Country Position/Affiliation
Cairo 19519 Egypt Emeritus Professor of General and Colorectal Surgery. Cairo University.
Role Name Email Phone Street address
Scientific Enquiries Nadia Ouda nadia.ouda@kasralainy.edu.eg +201225550500 Manial street
City Postal code Country Position/Affiliation
Cairo 35855 Egypt Head of Department of Bacteriology and Human immunology.
Role Name Email Phone Street address
Public Enquiries Hala Salah hala.salah@kasralainy.edu.eg +201001447705 Manial street
City Postal code Country Position/Affiliation
Cairo 35855 Egypt Dean of the faculty of Medicine and Professor of paediatrics.
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All the participants data collected during the trial will be available after deidentification. Analytic Code,Clinical Study Report,Informed Consent Form,Study Protocol After publication. Open access, raw data and data analysis, Through the main investigator, the Faculty of Medicine board will be a third party in this IPD according to qualifications and quality of the request.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://medicine.cu.edu.eg/index.php/en/departments/36-microbiology6 No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 08/05/2020 edit Epigenetics had been used successfully in the treatment of Viruses such as HIV and HCMV. Folic acid is known to correct epigenetic methylation pathway (1). Folic acid had been used to correct methylation defects through epigenetic pathway in prevention of Neural tube defects such as spina bifida an is recommended by the FDA to be given as 600 micro-gram in pregnant females which prove the safety of the medication. It is also used in prevention of precancerous colonic lesions such as Polyps in addition to other therapeutic uses(2). COVID-19 damages the immune system and organs through epigenetics and methylation pathway (3). In this study we suggest the use of Folic Acid stabilizes the DNA of human beings through methylation of the chromatin reader sites of the histone through epigenetic route which is the main site of action of COVID-19. Another study from Iran suggested the use of Folic acid in prevention and treatment of COVID-19 cases and proved that it decreases the intracellular transport of the virus through a trans-membrane protein called Furin (4). This study aims at detection of role of folic acid in prevention and control of COVID-19. Zeina Nehme, Sébastien Pasquereau and Georges Herbein: Control of viral infections by epigenetictargeted therapy. Nehme et al. Clinical Epigenetics (2019) 11:55 https://doi.org/10.1186/s13148-019-0654-9 2. Krista S. Crider, Thomas P. Yang, Robert J Berry, and Lynn B. Bailey: Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate’s Role. Nehme et al. Clinical Epigenetics (2019) 11:55 https://doi.org/10.1186/s13148-019-0654-9 3. https://www.whatisepigenetics.com/a-look-into-the-epigenetics-of-a-coronavirus-infection/ 4. Zahra Sheybani, Maryam Heydari Dokoohaki, Manica Negahdaripour, Mehdi Dehdashti, Hassan Zolghadr, Mohsen Moghadami, Seyed Masoom Masoompour, Amin Reza Zolghadr: The Role of Folic Acid in the Management of Respiratory Disease Caused by COVID-19. March 2020. doi.org/10.26434/chemrxiv.12034980.v1 Epigenetics had been used successfully in the treatment of Viruses such as HIV and HCMV. Folic acid is known to correct epigenetic methylation pathway (1). Folic acid had been used to correct methylation defects through epigenetic pathway in prevention of Neural tube defects such as spina bifida an is recommended by the FDA to be given as 600 micro-gram in pregnant females which prove the safety of the medication. It is also used in prevention of precancerous colonic lesions such as Polyps in addition to other therapeutic uses(2). COVID-19 damages the immune system and organs through epigenetics and methylation pathway (3). In this study we suggest the use of Folic Acid stabilizes the DNA of human beings through methylation of the chromatin reader sites of the histone through epigenetic route which is the main site of action of COVID-19. Another study from Iran suggested the use of Folic acid in prevention and treatment of COVID-19 cases and proved that it decreases the intracellular transport of the virus through a trans-membrane protein called Furin (4). This study aims at detection of role of folic acid in prevention and control of COVID-19. 1. Zeina Nehme, Sébastien Pasquereau and Georges Herbein: Control of viral infections by epigenetictargeted therapy. Nehme et al. Clinical Epigenetics (2019) 11:55 https://doi.org/10.1186/s13148-019-0654-9 2. Krista S. Crider, Thomas P. Yang, Robert J Berry, and Lynn B. Bailey: Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate’s Role. Nehme et al. Clinical Epigenetics (2019) 11:55 https://doi.org/10.1186/s13148-019-0654-9 3. https://www.whatisepigenetics.com/a-look-into-the-epigenetics-of-a-coronavirus-infection/ 4. Zahra Sheybani, Maryam Heydari Dokoohaki, Manica Negahdaripour, Mehdi Dehdashti, Hassan Zolghadr, Mohsen Moghadami, Seyed Masoom Masoompour, Amin Reza Zolghadr: The Role of Folic Acid in the Management of Respiratory Disease Ca
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 08/05/2020 edit Experimental Group, Folic acid oral tablet., 500-1000 micro gram per day as a single or divided doses., 4 weeks., 3 population: 1. Health care works at risk while caring for COVID-19 carriers and cases. This poulation include: Control group: will receive the already established protocols for prevention. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. 2. Asymptomatic carriers with positive PCR.This poulation include: Control group: will receive the already established protocols for treatment. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. 3. Non-critical symptomatic COVID-!9 cases diagnosed by PCR. This poulation include: Control group: will receive the already established protocols for treatment. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. , 30, Experimental Group, Folic acid oral tablet., 500-1000 micro gram per day as a single or divided doses., 4 weeks., 3 population: 1. Health care works at risk while caring for COVID-19 carriers and cases. This poulation include: Control group: will receive the already established protocols for prevention. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. 2. Asymptomatic carriers with positive PCR.This poulation include: Control group: will receive the already established protocols for treatment. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. 3. Non-critical symptomatic COVID-!9 cases diagnosed by PCR. This poulation include: Control group: will receive the already established protocols for treatment. Intervention group: will receive Folic Acid "oral supplements' as 500-1000 micro gram per day as a single or divided doses. , 30,
Section Name Field Name Date Reason Old Value Updated Value
Study Design Intervention assignment 08/05/2020 To save time. Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Parallel: different groups receive different interventions at same time during study
Section Name Field Name Date Reason Old Value Updated Value
Sponsors Sponsors List 08/05/2020 adding the postal Code. Faculty of Medicine Cairo university, Manail street., Cairo, , Egypt, Primary Sponsor, University, Faculty of Medicine Cairo university, Manail street., Cairo, 35855, Egypt, Primary Sponsor, University,
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 08/05/2020 to add the complete address and the PO code. Nadia Hafez Ouda and Hala Salah Eldin., Manial street, Cairo, , Egypt Nadia Hafez Ouda and Hala Salaf Eldin., Department of Microbiology. Faculty of Medicine. Cairo University, Almanial street 1, Cairo, 35855, Egypt
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 08/05/2020 Registering each co-author separately. Nadia Hafez Ouda and Hala Salah Eldin., Manial street, Cairo, , Egypt Nadia Hafez Ouda , Department of Microbiology. Faculty of Medicine. Cairo University, Almanial street 1, Cairo, 35855, Egypt
Section Name Field Name Date Reason Old Value Updated Value
Reporting Plan to share IPD 08/05/2020 As requested by the PACTR registry administration. Undecided Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 08/05/2020 As requested by the PACTR registry administration. All the participants data collected during the trial will be available after deidentification.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 08/05/2020 As requested by the PACTR registry administration. After publication.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 08/05/2020 As requested by the PACTR registry administration. Open access, raw data and data analysis, Through the main investigator, the Faculty of Medicine board will be a third party in this IPD according to qualifications and quality of the request.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD URL 08/05/2020 As requested by the PACTR registry administration. https://medicine.cu.edu.eg/index.php/en/departments/36-microbiology6
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 08/05/2020 As requested by the PACTR registry administration. Study Protocol, Informed Consent Form, Clinical Study Report, Analytic Code