The Efficacy of Nigella Sativa Versus VitaminD3 as Supplement Therapy in Coronavirus Disease 2019 (COVID-19)

Study Overview
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Brief Summary
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The aim this study is to investigate the safety and efficacy of Nigella Sativa versus Vitamin D3 versus Nigella Sativa / vitamin D3 combination as supplement for management of COVID-19 .

Detailed Description
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Corona-virus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2, and this virus was first originated from Wuhan city of Hubei province of China spreading around the globe. The prominent symptoms of COVID-19 include fever, cough, dyspnea, and other symptoms noted in patients affected by COVID-19 that includes; chills, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell. In addition, the emergency warning signs of COVID-19 include difficulty breathing or shortness of breath, persistent pain or pressure in the chest, new confusion or inability to arouse and bluish lips or face and the patients experiencing any of these signs should get immediate medical attention. Herbal medicines are used by many people to try to improve their health upon the believe that natural products are always safe, and good for immunity based on the traditional knowledge .There is a potential of Nigella Sativa to treat the patients with COVID-19. Nigella Sativa (NS), a widely used medicinal plant of the family Ranunculaceae ; commonly known as Black Cumin, has been shown to exert antiviral effects against a variety of viruses such as Mouse Cytomegalovirus and Hepatitis C Virus (HCV) . The components' antimicrobial properties against various microbes as well as their anti-inflammatory and immuno-modulatory effects have also been established . The immune system defends the body from foreign, invading organisms, promoting protective immunity, while maintaining tolerance to self. The implications of vitamin deficiency on the immune system have become clearer in recent years, and in the context of vitamin D deficiency, the increased susceptibility to infection observed, especially in a genetically susceptible host to autoimmunity. The classical actions of vitamin D are to promote calcium homeostasis, and to promote bone health. In humans, vitamin D is obtained from the diet, or synthesized in the skin as vitamin D is cutaneously produced after exposure to UV light, its synthesis is influenced by latitude, season, use of sun-block and skin pigmentation. Melanin absorbs UV radiation inhibiting the synthesis of vitamin D from 7-dihydrocholesterol. This initial vitamin D compound is inactive form; hydroxylation in the liver to form the active 25 hydroxy vitamin D3 (25 D). Vitamin D is the most reliable measurement of an individual's vitamin D status. It is converted in the kidney to the active compound 1,25 dihydroxy vitamin D (1,25 D) or calcidiol by 1-α-hydroxylase (CYP27B1), an enzyme which is stimulated by parathormone. A principal defense against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs). Treg levels have been reported to be low in many COVID-19 patients, and can be increased by vitamin D supplementation. Low vitamin D levels have been associated with an increase in inflammatory cytokines, and a significantly increased risk of pneumonia, and viral upper respiratory tract infections.

Official Title
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Evaluation of The Efficacy of Nigella Sativa Versus VitaminD3 as Supplement Therapy in Management of Coronavirus Disease 2019 (COVID-19)

Conditions
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Covid19

Intervention / Treatment
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* Dietary Supplement: Nigella Sativa capsule twice daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with mild-moderate COVID-19 according to the classification (Table 1) Adult (18 - 65 years old). Polymerase chain reaction (PCR)-confirmed infection with Severe Acute Respiratory Syndrome Coronavirus-2. Exclusion Criteria: Patients with severe illness requiring admission to intensive care unit. Asymptomatic patients. Severe chronic kidney disease (i.e. estimated glomerular filtration rate < 30 mL/min) or end stage renal disease requiring dialysis Severe chronic liver disease (Alanine transaminase or Aspartate transaminase > 5 times the upper limit of normal). contraindications to any of the interventional drugs. Pregnancy or breast feeding. Allergy to any of the interventional.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Controlled Parallel Open label Randomized Clinical Trial .
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: group 1<br>Twenty five patients will be administered only the standard treatment regimen according to Ministry Of Health, and Population management protocol for COVID-19 patients (November 2020). | |
| Active Comparator: group 2<br>Twenty five patients will be administered a single dose (900mg) of Nigella Sativa capsule twice daily plus standard therapy | Dietary Supplement: Nigella Sativa capsule twice daily<br>* investigate the safety and efficacy of Nigella Sativa versus Vitamin D3 versus Nigella Sativa / vitamin D3 combination as supplement for management of COVID-19 .<br>* Other names: single dose of vitamin D3 tablet (2000 IU) once daily;|
| Active Comparator: group 3<br>Twenty five patients will be administered a single dose (2000 IU) of vitamin D3 tablet once daily plus standard therapy | Dietary Supplement: Nigella Sativa capsule twice daily<br>* investigate the safety and efficacy of Nigella Sativa versus Vitamin D3 versus Nigella Sativa / vitamin D3 combination as supplement for management of COVID-19 .<br>* Other names: single dose of vitamin D3 tablet (2000 IU) once daily;|
| Active Comparator: group 4<br>Twenty five patients will be administered a single dose (900 mg) of Nigella Sativa capsule twice daily, and single dose of vitamin D3 tablet (2000 IU) once daily plus standard therapy. | Dietary Supplement: Nigella Sativa capsule twice daily<br>* investigate the safety and efficacy of Nigella Sativa versus Vitamin D3 versus Nigella Sativa / vitamin D3 combination as supplement for management of COVID-19 .<br>* Other names: single dose of vitamin D3 tablet (2000 IU) once daily;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and efficacy of Nigella Sativa and Vitamin D3 as a supplement for management of COVID-19 will be evaluated and recorded. | The patient will be examined by the physician and the rate of occurrence of any of the following signs and symptoms on the participants will be reported: Fever -Runny nose - Red swollen eyes Fatigue - Shortening in breath - Skin rash Cough - Body aches Sore throat - Diarrhea, and/or Vomiting Headache - Loss of taste and/or Smell | baseline and 14 days | 
| Assessment of patient health status before and after treatment intervention for a period of 14 days will be done | All patients will be evaluated during the study period (14 days) by undergoing PCR test after two days from absence of any clinical presentation, Then if the PCR is negative, the patient will be discharged from the hospital and complete his medication course at home. If the result is positive then the patient will undergo another PCR testing on day 14 with no further follow up . | baseline and 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The recovery rate of patients, Intensive care unit admission rate of patients and the Length of hospital stay of the patients will be recorded | Length of hospital stay and number of patients need ICU admission due to deterioration of cases and progression of disease. | 14 days | 
| The following laboratory testing will be performed at least twice during the study period: | C-Reactive Protein in mg/L. Arterial Blood Gases[carbon dioxide partial pressure, oxygen partial pressure] in mm Hg. Kidney function [serum creatinine, blood urea nitrogen ] in mg/dL. liver function [ Alanine aminotransferase, Aspartate aminotransferase] in IU/L . Erythrocyte sedimentation rate in mm/hr. Complete blood picture. Serum Ferritin in ug/L international normalized ratio, prothrombin time, partial thromboplastin time in seconds Polymerase chain reaction (PCR). Computed tomography (CT) chest . Length of hospital stay and number of patients need ICU admission due to deterioration of cases and progression of disease. | 14 days |