Low vs. Moderate to High Dose Vitamin D for Prevention of COVID-19

NCT04868903 | Completed Results DMC

• 1 other identifier: UChicagoBSDIRB20-1302
• Study Type: interventional
• Target: 1,475
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to compare the risks of COVID-19 in individuals from Chicagoland communities randomized to low (400 IU/day) vs. moderate (4,000 IU/day) or high (10,000 IU/day) dose vitamin D.

Conditions

SARS-CoV-2 Infection

Outcome Measures

Primary Outcomes (1)

• SARS-CoV-2 Infection as Measured by Patient Report of Clinically Confirmed COVID-19 (or Viral PCR When Available)

  For this outcome, hazard models will be employed to assess the effect of each vitamin D dosing strategy on the outcome. We will first develop hazard ratios for between-group analyses on the primary outcome using log-rank tests, and then develop Cox proportional hazard models to model the hazard function on a set of covariates including but not limited to, moderate or high vitamin D dose, baseline vitamin D levels, age, gender, race, ethnicity, sun exposure, sleep habits, exposure of cohabitants, job type, and study site. We will also control for randomization date to adjust the underlying hazard function for COVID-19 prevalence over time. While our primary analysis will pool subjects randomized to either the moderate or high dose and compare them to low dose subjects, we will also perform secondary analyses comparing low to moderate and low to high and additional analyses that use post randomization vitamin D levels as time varying covariates.

  Up to 9-months

Other Outcomes (4)

• Hospitalization Following COVID-19

  9 months

• ICU Stay Following COVID-19

  9 months

• Ventilator Use Following COVID-19

  9 months

Study Arms (3)

Low Dose Vitamin D

ACTIVE COMPARATOR

Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for 9 continuous months.

Dietary Supplement: Vitamin D3

Medium Dose Vitamin D

ACTIVE COMPARATOR

Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for 9 continuous months.

Dietary Supplement: Vitamin D3

High Dose Vitamin D

ACTIVE COMPARATOR

Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for 9 continuous months.

Dietary Supplement: Vitamin D3

Interventions

Vitamin D3 DIETARY_SUPPLEMENT

Half the subjects will be randomized to the low dose vitamin D therapy (400 IU/day), which will serve as the control group, and half to moderate (4,000 IU/day) or high (10,000 IU/day). Study participants will have the option between being randomized to the low versus moderate or the low versus high dose arms.

High Dose Vitamin D; Low Dose Vitamin D; Medium Dose Vitamin D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

Subjects are able to participate if they: 1. Are 18 years or older. 2. Live or work in the Chicagloland area (Illinois counties: Cook, Lake, McHenry, DuPage, Kane, Kendall, Grundy, Will, and Kankakee; Indiana counties: Lake and Porter). 3. Are interested in vitamin D as a potential preventive measure against COVID-19 in which they self-administer a daily dose of vitamin D during the 9-month study period. 4. Are willing to attend the laboratory for drop-in appointments at UChicago Medicine or Rush University Medical Center every 3 months at 4 time points over a 9-month period for blood draws measuring COVID-19 antibodies, calcium, vitamin D and PTH levels. 5. Are willing to complete self-report measures at 4 time points over the course of 9 months by completing a 15-minute survey at intake by telephone or via web and 10-minute web-based follow-up surveys. Subjects are excluded from study participation if they: 1. Report ever having a positive COVID-19 PCR test result 2. Report being pregnant, planning to become pregnant, and/or report breastfeeding during the study period. 3. Report a history of chronic kidney disease, including a history of abnormal GFR and/or creatinine. 4. Report a history of hyperparathyroidism. 5. Report a history of increased falls. 6. Report a history of hypercalcemia. 7. Report a history of gastrointestinal absorptive disorders, including having undergone bariatric surgery. 8. Report a history of kidney stones (1 in past year or 2 in lifetime). 9. Report already taking more than 400 IU of vitamin D daily as recommended by their health care provider, excluding multivitamins and excluding supplements that include vitamin D and calcium together. 10. Report taking D2. 11. Report a history of sarcoidosis. 12. Screen positive for hypercalcemia during the initial blood test or follow-up blood tests. 13. Screen positive for primary hyperparathyroidism during the initial blood test. 14. Screen positive for COVID-19 antibodies during the initial blood test. 15. Have vitamin D levels of \>100ng/mL at study start, or \>250ng/mL during follow-up labs. 16. Are unwilling to provide blood samples during quarterly blood tests. 17. Are unwilling to take daily vitamin D.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Chicago: lead
• Rush University Medical Center: collaborator

Study Sites (2)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637-1622, United States

Location

Related Publications (4)

• Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020 Apr 2;12(4):988. doi: 10.3390/nu12040988.

  PMID: 32252338 BACKGROUND

• Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583. doi: 10.1136/bmj.i6583.

  PMID: 28202713 BACKGROUND

• Meltzer DO, et al. "Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence. medRxiv. 2020 May 8.

  BACKGROUND

• McCullough PJ, Lehrer DS, Amend J. Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience. J Steroid Biochem Mol Biol. 2019 May;189:228-239. doi: 10.1016/j.jsbmb.2018.12.010. Epub 2019 Jan 4.

  PMID: 30611908 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Limitations and Caveats

Power was limited for high versus low dose. Sample size and multiplicity limit power to assess treatment heterogeneity, which helps contextualize the variable findings of supplementation studies. Results may not generalize to longer treatment durations, repeat infections, or other infections.

Results Point of Contact

• Title: David Meltzer, MD, PhD
• Organization: The University of Chicago

dmeltzer@bsd.uchicago.edu

7737020836

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2,000-person two-arm, double-blinded randomized controlled trial, with half the subjects randomized to low dose vitamin D therapy (400 IU/day), which will serve as the control group, and half to moderate (4,000 IU/day) or high (10,000 IU/day).

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: May 3, 2021
• Study Start: November 30, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 20, 2026
• Results First Posted: December 10, 2025

Record last verified: 2026-02

Locations

US (2)