Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of vitamin D and/or zinc supplementation on improving COVID-19 treatment outcomes. The effects of vitamin D, zinc, and both vitamin D and zinc together will be investigated among COVID-19 patients in India.

Detailed Description
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This study is a 2x2 factorial randomized double-blind, placebo-controlled trial to examine the effectiveness of vitamin D and zinc supplements as immune-based therapy among COVID-19 patients in India. The study is also examining the immunological response to COVID-19 and the effect of the intervention on specific biomarkers of immune and endothelial activation that are independent and quantitative predictors of severity and mortality in other severe infections. The primary aims are to determine the effect of vitamin D supplementation versus placebo on time to recovery among patients hospitalized with COVID-19; and to determine the effect of zinc supplementation versus placebo on time to recovery among patients hospitalized with COVID-19. As secondary aims, this study is also investigating the effect of vitamin D or zinc supplementation on all-cause mortality. necessity for assisted ventilation, individual symptoms duration, duration of hospital stay and biomarkers including vitamin D, Zinc, Interleukin 6 (IL-6), Angiopoietin-2, sTREM-1, immunoglobulin G (IgG) and immunoglobulin M (IgM). Eligible individuals are randomly assigned to one of four groups: (1) Vitamin D (180,000 IU bolus at enrollment, followed by 2000 IU daily); (2) Zinc (placebo at enrollment followed by one daily dose of 40 mg); (3) Vitamin D and Zinc; or (4) Placebo. Daily supplements start at the hospital and continue after discharge for a total of 8 weeks. Active data collection occurs daily while patients are hospitalized and at least twice per week via telephone after discharge. A clinical exam occurs at 8 weeks and longer-term symptoms are assessed at 3 months.

Official Title
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A Randomized Trial to Determine the Effect of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India

Conditions
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COVID-19

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 (cholecalciferol)
* Dietary Supplement: Zinc (zinc gluconate)
* Dietary Supplement: Zinc (zinc gluconate) & Vitamin D (cholecalciferol)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged >=18 years old Polymerase chain reaction (PCR) or Rapid Antigen Test (RAT)-confirmed infection with SARS-COV2 Provide informed consent Exclusion Criteria: Pregnancy Enrollment in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Interventional Model Description: The effect of both interventions (vitamin D or zinc) will be investigated simultaneously using a factorial design.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo- Placebo<br>Participants in the PLACEBO-PLACEBO group will receive a placebo vitamin D bolus at the hospital followed by placebo daily vitamin D maintenance doses and placebo daily zinc supplements. | Other: Placebo<br>* Placebo vitamin D bolus at enrollment followed by placebo daily vitamin D maintenance doses and placebo daily zinc supplements.<br>|
| Experimental: Vitamin D- Placebo<br>Participants in the VITAMIN D-PLACEBO group will receive an actual vitamin D bolus at the hospital followed by actual daily vitamin D maintenance doses and daily placebo zinc supplements. | Dietary Supplement: Vitamin D3 (cholecalciferol)<br>* 180,000 international units (IU) of vitamin D3 at enrollment, followed by 2000 IU once per day from enrollment to 8 weeks<br>|
| Experimental: Placebo-Zinc<br>Participants in the PLACEBO-ZINC group will receive a placebo vitamin D bolus at the hospital followed by placebo daily vitamin D maintenance doses and actual daily zinc supplements. | Dietary Supplement: Zinc (zinc gluconate)<br>* 40mg of zinc gluconate taken once per day from enrollment to 8 weeks<br>|
| Experimental: Vitamin D- Zinc<br>Participants in the VITAMIN D-ZINC group will receive an actual vitamin D bolus at the hospital followed by actual daily vitamin D maintenance doses and actual daily zinc supplements. | Dietary Supplement: Zinc (zinc gluconate) & Vitamin D (cholecalciferol)<br>* 180,000 IU of vitamin D3 at enrollment, followed by 2000 IU of vitamin D3 and 40mg of zinc gluconate once per day from enrollment to 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recovery | Defined as resolution of fever, cough and shortness of breath relative to baseline | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | Up to 8 weeks | 
| Necessity for assisted ventilation |  | Up to 8 weeks | 
| Individual symptoms duration |  | Up to 8 weeks | 
| Vitamin D |  | At 8 weeks | 
| Zinc |  | At 8 weeks | 
| Interleukin 6 (IL-6) |  | At 8 weeks | 
| Angiopoietin-2 |  | At 8 weeks | 
| sTREM-1 |  | At 8 weeks | 
| Immunoglobulin M (IgM) |  | At 8 weeks | 
| Immunoglobulin (IgG) |  | At 8 weeks | 
| Duration of hospital stay |  | Up to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Vitamin-D3, Zinc, Nutrition support, Host-directed therapy, Clinical management, India