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Vitamin D Supplementation in the Prevention and Mitigation of COVID-19 Infection (VitD-COVID19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04482673
Recruitment Status : Recruiting
First Posted : July 22, 2020
Last Update Posted : August 4, 2020
Sponsor:
Collaborators:
Grassroots Health Nutrition Institute
ZRT Laboratory
Information provided by (Responsible Party):
Carol L. Wagner, MD, Medical University of South Carolina

Tracking Information
First Submitted Date  ICMJE July 1, 2020
First Posted Date  ICMJE July 22, 2020
Last Update Posted Date August 4, 2020
Actual Study Start Date  ICMJE July 31, 2020
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 21, 2020)
  • Change in total circulating 25(OH)D concentration [ Time Frame: monthly in COVID-19 negative participants through study completion for 1 year ]
    metabolite of vitamin D
  • Change in total circulating 25(OH)D concentration in COVID-19 positives [ Time Frame: baseline, 2 and 4 weeks, then months 3, 6, 9 and 12 in COVID-19 positive participants ]
    metabolite of vitamin D
  • Change in SARS-CoV-2 antibody titers [ Time Frame: every 3 months up to 12 months ]
    The presence or absent of SARS-CoV-2 antibody will be measured at baseline, 3, 6, 9 and 12 months.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2020)
  • Change in inflammatory cytokine concentration (10 cytokine panel Elisa: Interferon (INF)-gamma, Interleukin (IL)-1beta, IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, IL-13, Tumor Necrosis Factor (TNF)-alpha [ Time Frame: baseline and every 3 months up to 12 months ]
    At baseline, 3, 6, 9 and 12 months, inflammatory cytokines will be measured in participant plasma samples. Cytokines to be measured are Interferon-gamma (IFN-g), Interleukin-1beta (IL-1B), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, and Tumor Necrosis Factor-alpha (TNFa). Values of these cytokines at baseline will compared to those at 3, 6, 9, and 12 months
  • Respiratory symptoms [ Time Frame: daily for 2 weeks ]
    COVID-19 positive participants or if COVID-19 negatives develop respiratory symptoms will complete this respiratory survey daily for 2 weeks
  • Signs and symptoms of rhino/sinusitis [ Time Frame: Baseline then 3, 6, 9 and 12 months in negatives and daily for 2 weeks in positives ]
    Inventory of signs and symptoms of rhino/sinusitis. These signs include sneezing, running nose, cough, dizziness, fatigue, and sense of smell. Each sign is rated on a scale of 0 to 5, with 0 indicating not problem, for instance 1 indicating mild problem, 4 indicating severe problem and 5 indicating problem as bad as it can be.
  • NCI Dietary Intake [ Time Frame: baseline then at 6 and 12 months ]
    Dietary intake assessment
  • Charlson Comorbidity survey [ Time Frame: baseline then at 6 and 12 months ]
    Survey of participant health problems
  • Paffenberger Physical Activity Assessment [ Time Frame: Baseline then at 6 and 12 months ]
    Assessment of physical activity of each participant
  • Perceived stress [ Time Frame: monthly for 1 year ]
    Each participant will complete the Perceived Stress Scale Questionnaire (PSS) to assess their perceived stress. Assessments are base on a scale of 0 to 4, with 0 indicating "never" and 4 indicating "very often"
  • Pandemic stress [ Time Frame: monthly for 1 year ]
    Each participant will complete the and Pandemic Stress Index Questionnaire (PSI) to assess their perceived stress cause by the pandemic. Assessments are base on a scale of 0 to 6, with 0 indicating "not at all" and 5 indicating "extremely," and 6 indicating "decline to answer."
  • NEO-Personality Inventory [ Time Frame: baseline visit ]
    Personality characteristics of each participant
  • GrassrootsHealth Monthly Health assessment [ Time Frame: baseline, 6, and 12 months ]
    A health assessment will be completed by each participant monthly for 1year. This health. This is for information on health status only and not for comparative assessment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vitamin D Supplementation in the Prevention and Mitigation of COVID-19 Infection
Official Title  ICMJE The Role of Vitamin D in Mitigating COVID-19 Infection Severity: Focusing on Reducing Health Disparities in South Carolina
Brief Summary The purpose of this study is to evaluate how useful vitamin D supplementation is in reducing the severity of COVID-19 symptoms and the body's inflammatory and infection-fighting response to COVID-19. Individuals ≥50 years of age and older who are tested for COVID-19 and negative will be randomized (like flipping a coin) to either daily high dose vitamin D supplementation (6000 IU vitamin D3/day) vs. standard of care. Those individuals ≥50 years of age or older who test positive for COVID-19 at baseline will be randomized to bolus vitamin D (20,000 IU/day for 3 days) followed by high dose (6000 IU vitamin D/day) vs. standard of care for 12 months. All participants will receive a multivitamin containing vitamin D.
Detailed Description

Vitamin D (vitD) deficiency is more prevalent among African Americans and Latinx and in the elderly who have low exposure to sunlight. African Americans and nursing home residents who contract SARS-CoV-2, the novel virus that first appeared in Wuhan, China, and who develop the disease designated COVID-19 experience a much worse clinical outcome than other groups. Some have speculated that low vitD status could exacerbate COVID-19 infection, especially if the viral infection reaches the lower respiratory tract.

Sufficient vitD may help to improve the pulmonary immune response to the virus, reduce the dangerous cytokine storm, and lessen surfactant dysregulation, potentially preventing or ameliorating the acute syndrome. To maximize the benefits of vitD on host response to SARS-CoV-2, prophylactic supplementation to ensure sufficiency before COVID-19 would be the preferable public health option. Yet, vitD supplementation during acute infection may also improve overall clinical outcome in some infected patients. It is a relatively inexpensive therapy that has a large safety profile when given in doses of 4000-6000 international units/day to adults.

To date, there is no effective cure or preventive vaccine for COVID-19. Given the risk of disease and death, any intervention that reduces the morbidity and mortality from COVID-19 would be of immense value. We hypothesize that achieving and sustaining vitD sufficiency through dietary supplementation will result in improved immune function and a decrease in COVID-19 incidence and symptomatology. Importantly, this objective will address the significant health disparity of vitD deficiency among black, Latina and the elderly. We further hypothesize that those individuals with a circulating 25(OH)D of ≥40 ng/mL will have less severe COVID-19 symptoms, particularly among higher risk populations. We will compare the effectiveness of higher dose vitD vs. standard of care dosing.To test these hypotheses, we propose the following Aims:

  1. Focusing on prevention, this Aim will test whether achieving vitD sufficiency (as defined by total circulating 25(OH)D ≥40-60 ng/mL) in individuals at risk for deficiency will improve clinical outcomes in those who subsequently develop COVID-19.
  2. Focusing on vitD as mitigation therapy, this Aim will evaluate the effectiveness of bolus dosing followed by daily vitD supplementation in achieving the target 25(OH)D range of ≥40-60 ng/mL in those individuals testing positive for COVID-19 at MUSC/affiliated hospital facilities, but do not require admission to a hospital (outpatient) and will examine whether achieving this target range is associated with less severe COVID-19 and differences in inflammatory cytokine profiles.

In the prevention arm of this project (Aim 1), individuals at higher risk ≥50 years of age who test negative for COVID-19 at MUSC/its affiliate hospitals, and agree to daily vitD supplementation for a 12-month period, with vitD status measured monthly will be randomized to placebo or prescribed vitD (6000 IU/day) to achieve a total circulating 25(OH) concentration of ≥40-60 ng/mL. We will compare study groups regarding subsequent infection with COVID-19, severity of symptoms, need and duration of hospitalization (LOS), admission to the ICU, need for ventilatory support, and mortality, along with return to baseline activities and/or work, as a function of age, BMI, and other recognized COVID-19 risk factors. In the mitigation arm of this project (Aim 2), non-hospitalized individuals ≥50 years of age who test COVID-19 positive will be randomized to placebo or a bolus of oral vitD (20,000 IU X 3 days) followed by 6000 IU vitD/day, and we will compare study groups on measures of disease severity as in Aim 1. All participants in both Aims 1 and 2 will receive a daily multivitamin (MVI) containing 800 IU VitD for the 12-month period.

Following the completion of these Aims, we will be able to answer the following questions:

  1. Are individuals with vitD deficiency more likely to be diagnosed with COVID-19 infection?
  2. Does being vitD replete make a person more likely to have asymptomatic COVID-19?
  3. Does vitD sufficiency status account for why African Americans, Latina, and the elderly more likely to experience complications related to COVID-19?
  4. Is vitD deficiency in COVID-19 positive outpatients associated with increased severity of symptoms and differences in inflammatory cytokine profiles that is mitigated by bolus and then sustained vitD supplementation?

The long-term impact of these studies will influence public policy regarding more widespread vitD supplementation is a means of reducing the severity of COVID-19. Given its low cost and the ease with which widespread supplementation could be instituted, oral vitD supplementation may represent a rapid and inexpensive means by which to reduce both the COVID-19 incidence and severity.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • COVID-19
  • Vitamin D Deficiency
  • Respiratory Viral Infection
Intervention  ICMJE
  • Drug: Daily Vitamin D3
    6000 IU vitamin D3 daily
    Other Name: Daily cholecalciferol
  • Drug: Daily placebo
    Placebo daily
  • Drug: Bolus vitamin D3
    Bolus 20,000 IU vitamin D3 daily for 3 days
    Other Name: Bolus cholecalciferol
  • Drug: Bolus placebo
    Bolus placebo daily for 3 days
Study Arms  ICMJE
  • Experimental: COVID-19 Negative Active Treatment
    Participants will be randomized to vitamin D3 (6000 IU) per day for 12 months. All participants will receive a multivitamin containing 800 IU vitamin D3/day.
    Intervention: Drug: Daily Vitamin D3
  • Placebo Comparator: COVID-19 Negative Placebo
    Participants in this arm would receive placebo for 12 months. All participants will receive a multivitamin containing 800 IU vitamin D3/day.
    Intervention: Drug: Daily placebo
  • Experimental: COVID-19 Positive Active Treatment
    Participants will be randomized to vitamin D3 as a bolus (20,000 IU) per day for 3 days followed by high dose vitamin D (6000 IU) per dayfor 12 months. All participants will receive a multivitamin containing 800 IU vitamin D3/day.
    Interventions:
    • Drug: Daily Vitamin D3
    • Drug: Bolus vitamin D3
  • Placebo Comparator: COVID-19 Positive Placebo
    Participants in this arm would receive placebo as a bolus followed by daily placebo for 12 months. All participants will receive a multivitamin containing 800 IU vitamin D3/day.
    Interventions:
    • Drug: Daily placebo
    • Drug: Bolus placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 21, 2020)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Entry Criteria:

---Adults aged 50 years of age or older who presents to MUSC or its affiliate hospitals (or associated testing centers) for COVID-19 testing during the recruitment period is eligible for participation.

Exclusion Criteria:

  • Hospitalization at the time of study recruitment.
  • Any individual less than 50 years of age. The reason that the participants ≥50 years are being excluded from this study is because those who are ≥50 years have a higher risk of being symptomatic with COVID-19 and have the potential for the greatest benefit. The disease appears to manifest differently in children and its occurrence is quite rare.
  • Only those patients tested for COVID-19 initially will be eligible to participate; therefore, anyone wanting to participate in the trial must have had a COVID-19 test prior to enrollment/participation in the study.
  • Any individual who is not capable of making independent decisions and who is considered cognitively impaired.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Carol L Wagner, MD 843-792-8829 washinro@musc.edu
Contact: Renee O Washington, MS 8437925884 washinro@musc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04482673
Other Study ID Numbers  ICMJE 00099939
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Carol L. Wagner, MD, Medical University of South Carolina
Study Sponsor  ICMJE Medical University of South Carolina
Collaborators  ICMJE
  • Grassroots Health Nutrition Institute
  • ZRT Laboratory
Investigators  ICMJE
Principal Investigator: Carol L Wagner, MD Medical University of South Carolina
PRS Account Medical University of South Carolina
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP