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

Phase 3

Completed

• Conditions: COVID-19
• Interventions: Other: Placebo; Dietary Supplement: Zinc (zinc gluconate); Dietary Supplement: Zinc (zinc gluconate) & Vitamin D (cholecalciferol); Dietary Supplement: Vitamin D3 (cholecalciferol)

• Registration Number: NCT04641195
• Lead Sponsor: Harvard School of Public Health (HSPH)

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-11-19
• Study First Submitted QC: 2020-11-20
• Study First Posted: 2020-11-23
• Study Start: 2021-04-22
• Primary Completion: 2022-07-01
• Study Completion: 2022-08-01
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-15
• Last Update Posted: 2022-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 181

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placebo- 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.
Placebo-Zinc	Zinc (zinc gluconate)	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.
Vitamin D- Zinc	Zinc (zinc gluconate) & Vitamin D (cholecalciferol)	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.
Vitamin D- Placebo	Vitamin D3 (cholecalciferol)	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.

Primary Outcome Measures

Name	Time	Method
Time to recovery	Up to 8 weeks	Defined as resolution of fever, cough and shortness of breath relative to baseline

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Saifee Hospital; 🇮🇳 Mumbai, Maharashtra, India

King Edward Memorial (KEM) Hospital; 🇮🇳 Pune, Maharashtra, India