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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Other: Placebo; Dietary supplement: Vitamin D3 (cholecalciferol); Dietary supplement: Zinc (zinc gluconate); Dietary supplement: Zinc (zinc gluconate) & Vitamin D (cholecalciferol)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Maharashtra
    • Mumbai, Maharashtra, India
      • Saifee Hospital
    • Pune, Maharashtra, India
      • King Edward Memorial (KEM) Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo- Placebo; 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; Placebo vitamin D bolus at enrollment followed by placebo daily vitamin D maintenance doses and placebo daily zinc supplements.
Experimental: Vitamin D- Placebo; 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); 180,000 international units (IU) of vitamin D3 at enrollment, followed by 2000 IU once per day from enrollment to 8 weeks
Experimental: Placebo-Zinc; 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); 40mg of zinc gluconate taken once per day from enrollment to 8 weeks
Experimental: Vitamin D- Zinc; 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); 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Harvard School of Public Health (HSPH)
• Collaborators: University Health Network, Toronto; Foundation for Medical Research
• Investigators: Principal Investigator: Wafaie W Wafaie, MBBS, MPH, MS, DrPH, Harvard School of Public Health (HSPH)

Publications and helpful links

General Publications

• Sharma KK, Partap U, Mistry N, Marathe Y, Wang M, Shaikh S, D'Costa P, Gupta G, Bromage S, Hemler EC, Kain KC, Dholakia Y, Fawzi WW. Randomised trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among patients with COVID-19 in India: trial protocol. BMJ Open. 2022 Aug 29;12(8):e061301. doi: 10.1136/bmjopen-2022-061301.

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2021
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; India; Zinc; Vitamin-D3; Nutrition support; Host-directed therapy; Clinical management
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Trace Elements; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols; Zinc
• Other Study ID Numbers: VR3- 172649

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No