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

July 2, 2026 updated by: University of Chicago
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study will recruit 2,000 subjects from the Chicagoland area to participate in the study at University of Chicago Medicine (UCM) and at Rush University (RU). Subjects will be invited to volunteer to participate in the study through a variety of forms of community outreach (flyers, presentations, emails, etc.). The sample size was chosen to have at least 80% power to detect a 25% or larger decrease in the hazard of developing COVID-19 between study arms at p<0.05 assuming a 30% baseline COVID-19 incidence rate over the study period, in line with a 3% per month incidence.

Subjects will take a daily dose of vitamin D, attend laboratory appointments for testing, and answer surveys over 9 months after enrollment.

Our overall aim is to compare the risks of COVID-19 in adults in the Chicagoland area at increased risk of COVID-19 randomized to low (400 IU/day) vs. moderate (4,000 IU/day) or high (10,000 IU/day) dose vitamin D. Our specific aims are:

Aim 1: To compare the risk of developing COVID-19 in adults in the Chicagoland area at increased risk of COVID-19 randomized to low vs. moderate or high dose vitamin D. Subjects will specify their preference for moderate versus high dose vitamin D and then be randomized between low dose vitamin D and their preferred moderate or high dose alternative. We hypothesize that moderate and high dose therapy will reduce rates of COVID-19 compared to low dose therapy because vitamin D will reduce symptomatic infection that prompts testing for COVID-19. Our primary analysis will pool subjects randomized to the moderate or high dose and compare them to low dose subjects, with secondary analyses comparing low to moderate and low to high.

Aim 2: To compare COVID-19 seroconversion in adults in the Chicagoland area at increased risk of COVID-19 randomized to low vs. moderate or high dose vitamin D. As we suspect the main effect of vitamin D may be to decrease symptomatic disease we hypothesize that there may be little or no difference in seroconversion.

Aim 3: To compare COVID-19 outcomes (hospitalization, ICU stay, ventilator use, death) in adults in the Chicagoland area at increased risk of COVID-19 randomized to low vs. moderate or high dose vitamin D. Consistent with several recent observational analyses, we expect higher doses to improve COVID-19 outcomes.

Additional aims examine the relationship between vitamin D and other markers of immune response:

Aim 4: Create a biobank of PBMCs from a panel of 500 individuals with well characterized levels of vitamin A and D. We propose to cryopreserve PBMCs derived from ~20 ml of blood to test the impact of vitamin A and D levels in the regulation of immune responses.

Aim 5: Evaluate the impact of vitamin A and D levels on immune function. We will perform immunophenotyping of PBMC using a panel of 30 antibodies that allow characterizing the different immune cell populations found in circulation, as well as their functional status. Using these data we will ask if there is an association between the prevalence of certain immune cell population or functional potential and vitamin A and D levels.

Aim 6: Evaluate the impact of vitamin A and D levels on PBMC gene expression levels. We will perform transcriptional profiling of PBMC from a panel of 100 individuals enriched for individuals on the two extremes of the distributions of vitamin A and D levels. These data will be used to identify changes in gene expression levels that differ between individuals showing low- vs high-vitamin A/D levels.

Aim 7: To test the hypothesis that oral vitamin D3 intervention will inhibit the renin- angiotensin system and reduce the incidence and/or severity of COVID-19 infections

Blood labs will be taken from subjects at intake, 3 months, 6 months and 9 months.

Intake labs will measure baseline calcium and PTH levels, COVID-19 antibodies, and vitamin D. Intake labs for a subset of University of Chicago Medicine (UCM) subjects will additionally measure vitamin A, vitamin D-binding protein (DBP), RAS components (Renin, Ang II, soluble ACE and ACE2), bradykinin, inflammation markers (IL-6, TNF-a, IL-1b and CRP), and SARS-CoV-2 antibodies against S-protein and N-protein.

3-month labs for all subjects will measure PTH, calcium, and vitamin D for monitoring of the intervention's safety and outcomes, and COVID-19 antibodies for monitoring of the outcome. 6-month and 9-month labs for all subjects will measure PTH, calcium, and vitamin D for monitoring of the intervention's safety and COVID-19 antibodies for monitoring of the outcome. Vitamin A will be measured for a subset of UCM subjects who were high at baseline.

Throughout the study period we will tell subjects about calcium, PTH and vitamin D lab results only if they suggest a safety concern for which we would like them to seek care. Subjects will be told if they test positive for COVID-19 antibodies. Except in the instance of a safety concern, subjects will be blinded to their vitamin A & D levels, calcium and PTH throughout the study to ensure protocol compliance. At the end of the study, we will inform subjects of their vitamin D levels. Electronic Medical Records will be reviewed for predictors and indicators of COVID-19 and for severity of infection if subject has had a positive COVID-19 test result.

Subjects will be asked to complete a web-based survey at intake, 3, 6 and 9 months. The intake survey will collect baseline data on subjects' current medications and supplements, sun exposure, Fitzpatrick skin type, exercise, diet and sleep habits, possible COVID-19 symptoms, and other influenza-like symptoms. Subjects will also be asked to report suspected exposure to the virus, occupation, and demographic information. Subjects will also be asked to evaluate risks of exposure. Follow-up surveys at months 3, 6, and 9 will ask the participant (or proxy) whether the participant has had a clinically confirmed diagnosis of COVID-19, and the date if so, ask about rates of study medication adherence, and assess for changes in the intake questions about use of other supplements, sun exposure, diet, exercise, and COVID-19 exposures. If the patient is reported to have had COVID-19, we ask about severity, including hospitalization and duration, ICU-use and duration, and need for mechanical ventilation and duration, death and COVID-19 symptom severity.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1475

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637-1622
        • University of Chicago

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Low Dose Vitamin D
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
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.
Active Comparator: Medium Dose Vitamin D
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
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.
Active Comparator: High Dose Vitamin D
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
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
SARS-CoV-2 Infection as Measured by Patient Report of Clinically Confirmed COVID-19 (or Viral PCR When Available)
Time Frame: Up to 9-months
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
SARS-CoV-2 antibody seroconversion confirmed by a COVID-19 antibody test
Time Frame: 9 months
We will use longitudinal mixed effects models to analyze this data that will provide measures only at the time of blood draws (3, 6 and 9 months). Covariates and secondary analyses will mirror those in the primary outcome measure.
9 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospitalization Following COVID-19
Time Frame: 9 months
This will be measured by a binary indicator of whether the patient is hospitalized after COVID-19 in the first quarterly survey after COVID-19 is reported and will be analyzed with a generalized linear model with covariates as in the secondary outcome measure.
9 months
ICU Stay Following COVID-19
Time Frame: 9 months
This will be measured by a binary indicator of whether the patient is admitted to the ICU after COVID-19 in the first quarterly survey after COVID-19 is reported and will be analyzed with a generalized linear model with covariates as in the secondary outcome measure.
9 months
Ventilator Use Following COVID-19
Time Frame: 9 months
This will be measured by a binary indicator of whether the patient receives mechanical ventilation after COVID-19 in the first quarterly survey after COVID-19 is reported and will be analyzed with a generalized linear model with covariates as in the secondary outcome measure.
9 months
Death Following COVID-19
Time Frame: 9 months
This will be measured by a binary indicator of whether the patient dies after COVID-19 in the first quarterly survey up to 9 months after COVID-19 is reported and will be analyzed with a generalized linear model with covariates as in the secondary outcome measure.
9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Chicago

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Rush University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 30, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 6, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 26, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 3, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UChicagoBSDIRB20-1302

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Uncertain if will share IPD. No plan determined.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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