[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100418606":3},{"organization":4,"armGroups":7,"interventions":35,"overallOfficials":56,"centralContacts":61,"locations":40,"responsibleParty":66,"collaborators":40,"id":69,"slug":70,"hasResults":71,"nctId":72,"briefTitle":73,"officialTitle":73,"acronym":74,"eligibilityCriteria":75,"healthyVolunteers":76,"sex":77,"minAge":78,"maxAge":79,"enrollmentInfo":80,"targetDuration":40,"studyType":83,"phases":84,"briefSummary":87,"conditions":88,"keywords":40,"overallStatus":90,"whyStopped":40,"lastUpdateSubmitDate":91,"lastUpdatePostDateStruct":92,"startDateStruct":95,"completionDateStruct":97,"leadSponsor":99,"locationsCount":40},{"fullName":5,"class":6},"Kafrelsheikh University","OTHER",[8,14,19,24,29],{"label":9,"type":10,"description":11,"interventionNames":12},"Oral 13 cis retinoic acid","EXPERIMENTAL","The participants will receive 13 cis retinoic acid (0.5 mg\u002Fkg\u002Fday in 2 divided doses orally for 14 days . All subjects were encouraged to complete the full course of treatment and common side effects were explained. Side effects and compliance will be documented.",[13],"Drug: Oral 13 cis retinoic acid",{"label":15,"type":10,"description":16,"interventionNames":17},"Aerosolized 13 cis retinoic acid","The participants will receive Aerosolized 13 cis retinoic acid in gradual in 2 divided doses increases froms 0.2 mg\u002Fkg\u002Fday to 4 mg\u002Fkg\u002Fday as inhaled 13 cis retinoic acid therapy for 14 days. All subjects were encouraged to complete the full course of treatment and common side effects were explained. Side effects and compliance will be documented.",[18],"Drug: Aerosolized 13 cis retinoic acid",{"label":20,"type":10,"description":21,"interventionNames":22},"13 cis retinoic acid doses orally in combination with spike protein based vaccine","The participants will receive 13 cis retinoic acid (0.5 mg\u002Fkg\u002Fday in 2 divided doses orally for 14 days and also, participants will receive two doses of spike protein based vaccine such as ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants will have 15 routine visits over a 24 month period.All subjects were encouraged to complete the full course of treatment and common side effects were explained. Side effects and compliance will be documented",[23],"Combination Product: 13 cis retinoic acid doses orally in combination with spike protein based vaccine",{"label":25,"type":10,"description":26,"interventionNames":27},"Aerosolized 13 cis retinoic acid in combination with spike protein based vaccine","The participants will receive Aerosolized 13 cis retinoic acid in gradual in 2 divided doses increases froms 0.2 mg\u002Fkg\u002Fday to 4 mg\u002Fkg\u002Fday as inhaled 13 cis retinoic acid therapy for 14 days and also, participants will receive two doses of 5-7.5x10\\^10 vp spike protein based vaccine such as ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants will have 15 routine visits over a 24 month period.All subjects were encouraged to complete the full course of treatment and common side effects were explained. Side effects and compliance will be documented",[28],"Combination Product: Aerosolized 13 cis retinoic acid in combination with spike protein based vaccine",{"label":30,"type":31,"description":32,"interventionNames":33},"spike protein based vaccine such as ChAdOx1 nCoV-19 vaccine","SHAM_COMPARATOR","The participants will receive two doses of 5-7.5x10\\^10 vp spike protein based vaccine such as ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants will have 15 routine visits over a 24 month period.All subjects were encouraged to complete the full course of treatment and common side effects were explained. Side effects and compliance will be documented",[34],"Biological: Biological: spike protein based vaccine such as ChAdOx1 nCoV-19 vaccine",[36,41,44,48,51],{"type":37,"name":9,"description":38,"armGroupLabels":39,"otherNames":40},"DRUG","Dose of 0.5 mg\u002Fkg\u002Fday in 2 divided doses orally for 14 days",[9],null,{"type":37,"name":15,"description":42,"armGroupLabels":43,"otherNames":40},"Dose of Aerosolized 13 cis retinoic acid in gradual in 2 divided doses increases froms 0.2 mg\u002Fkg\u002Fday to 4 mg\u002Fkg\u002Fday",[15],{"type":45,"name":20,"description":46,"armGroupLabels":47,"otherNames":40},"COMBINATION_PRODUCT","Dose of 13 cis retinoic acid (0.5 mg\u002Fkg\u002Fday in 2 divided doses orally for 14 days and also, participants will receive two doses of 5-7.5x10\\^10 vp spike protein based vaccine such as ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart",[20],{"type":45,"name":25,"description":49,"armGroupLabels":50,"otherNames":40},"Dose of Aerosolized 13 cis retinoic acid in gradual in 2 divided doses increases from 0.2 mg\u002Fkg\u002Fday to 4 mg\u002Fkg\u002Fday for 14 days and also, participants will receive two doses of 5-7.5x10\\^10 vp spike protein based vaccine such as ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart",[25],{"type":52,"name":53,"description":54,"armGroupLabels":55,"otherNames":40},"BIOLOGICAL","Biological: spike protein based vaccine such as ChAdOx1 nCoV-19 vaccine","Dose of 5-7.5x10\\^10vp of spike protein based vaccine such as ChAdOx1 nCoV-19 in deltoid of non-dominant arm, 28 days apart",[30],[57],{"name":58,"affiliation":59,"role":60},"Mahmoud Elkazzaz, M.Sc in Biochemistry","Facculty of Science, Damietta University","PRINCIPAL_INVESTIGATOR",[62],{"name":58,"role":63,"phone":64,"phoneExt":40,"email":65},"CONTACT","00201090302015","mahmoudramadan2051@yahoo.com",{"type":60,"investigatorFullName":67,"investigatorTitle":68,"investigatorAffiliation":5,"oldNameTitle":40,"oldOrganization":40},"Mahmoud Ramadan mohamed Elkazzaz","Faculty of Science, Damietta University","100418606","phase-1-investigating-the-role-of-13cis-retinoic-acid-in-the-treatment-of-covid-19-and-enhancement-of-its-spike-protein-based-vaccine-efficacy-and-safety-100418606",false,"NCT04730895","Investigating the Role of 13cis Retinoic Acid in the Treatment of COVID-19 and Enhancement of Its Spike Protein Based Vaccine Efficacy and Safety.","Isotretinoin","Inclusion Criteria:\n\n1. Healthy adults aged 18-40 years.\n2. Increased risk of SARS-CoV-2 infection\n3. Medically stable\n\nExclusion Criteria:\n\n1. Confirmed or suspected immunosuppressive or immunodeficient state\n2. Prior or concomitant vaccine therapy for COVID-19\n3. significant disease, disorder, or finding\n4. Hypercholesterolemia\n5. Hypertriglyceridemia\n6. Liver disease\n7. Renal disease\n8. Sjögren syndrome\n9. Pregnancy\n10. Lactation\n11. Depressive disorder\n12. Body mass index less than 18 points or higher than 25 points\n13. Contraindications for hormonal contraception or intrauterine device.\n14. Autoimmune diseases A history of organ, bone marrow or hematopoietic stem cell transplantation\n15. Patients receiving anti-hcv treatment\n16. Permanent blindness in one eye\n17. History of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery\n18. The competent physician considered it inappropriate to participate in the study\n\n    \\-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n\nSafety and promising features of isotretinoin in tne era of COVID 2019 according Principal Investigator Protocol:\n\n1. This medication have the feature of Aerosolized Drug Delivery to increase its efficacy beside Oral administration, Which makes it distinct from other medication in which should dose be only given orally. A study demonstrated that treating with 13 cis retinoic acid aerosolized via inhalation rout did not cause any damage in lung cells.\n2. Repeated high doses of 13 cis retinoic by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. The results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lung.\n3. Inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity.\n4. A study demonstrated that 13 cis retinoic is used in treating Emphysema (emphysema is a lung condition that causes shortness of breath)\n5. RA has been reported to induce formation of new alveoli and returns elastic recoil in the lung to approximately normal values in animal models of emphysema.\n6. Strong expectation of complete COVID -19 blockade from cell entry and infection depending on strong ethics, researches and references.\n7. Availability of our compounds.\n8. Ease of application.\n9. Expectation of COVID -19 treating by isotretinoin via more than one distinct mechanism.\n10. Inhibiting of thrombosis and platelet which is the most serious consequences caused by viral spike protein or vaccine spike protein:- Co-incubation with 13-cis-RA and IL-1 resulted in a synergic increase in the release of Prostacyclin Synthase (PGI2). PGI is a powerful vasodilator that inhibits platelet aggregation through activation of adenylate cyclase,Consistently 13-cis-RA increased the ability of HUVEC to inhibit Arachidonic acid -induced platelet aggregation. Because of 13cRA is a synthetic form that may function similar to the other produced isoforms, or by isomerization to atRA and 9c RA. RA therapy has proven anti-platelet , anti- inflammatory, and fibrinolytic activities we suggest that 13cRA may protect patients infected with covid-19 from pulmonary clots.\n11. Isotretinoin can induce Innate Immune response for recognition of CoV in addition to , inhibiting IL-6 The genome of Middle East Respiratory Syndrome Coronavirus is recognized by melanoma differentiation-associated protein-5 (MDA5), retinoic acid inducible gene-1 (RIG-1) and endosomal toll-like receptor 3 (TLR3) as pathogen-associated molecular patterns which recognize ssRNA and dsRNA intermediate of COVID-19.This recognition resulted in the formation of type-1 interferon (IFN1) as in (fig 6).COVID-19 synthesizes proteins that hinder the production IFN1 in its replication pathway, which is an evasion mechanism \\[123\\],\\[124\\],\\[125\\],\\[126\\],\\[127\\],\\[128\\],\\[129\\]. A study demonstrated that TLR3(-\u002F-), TLR4(-\u002F-), and TRAM(-\u002F-) mice are more susceptible to SARS-CoV than wild-type mice but experience only transient weight loss with no mortality in response to infection. On the other hand, mice deficient in the TLR3\u002FTLR4 adaptor TRIF are highly susceptible to SARS-CoV infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers \\[130\\]. Previous studies revealed that the high level of IFN- α\u002Fβ produced via the TLR3-IRF3\u002FIRF7 pathway and IFN-β is the reason for inhibiting Dengue virus (DENV) replication \\[131\\]. 13-cis retinoic acid induced significant upregulation of toll-like receptor 3 (TLR3), mitochondrial antiviral-signaling protein (MAVS) and (RIG-I) and IFN regulatory factor 1 expression in a time-dependent \\[132\\].Furthermore, A study reported that 13-cis-retinoic acid and other retinoid analogs inhibit IL-1-induced IL-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated. This effect was dose-dependent with an IC50 of 10(-7) M RA and significant inhibition was found with doses of RA as low as 10(-8) M \\[122\\].",true,"MALE","18 Years","40 Years",{"count":81,"type":82},360,"ESTIMATED","INTERVENTIONAL",[85,86],"PHASE1","PHASE2","Investigating the role of 13cis retinoic acid in the treatment of COVID-19 and enhancement of Its spike protein based vaccine efficacy and safety.",[89],"Covid19 Vaccine","UNKNOWN","2021-05-28",{"date":93,"type":94},"2021-06-02","ACTUAL",{"date":96,"type":82},"2021-07",{"date":98,"type":82},"2023-12",{"name":5,"class":6}]