<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04482673</url>
  </required_header>
  <id_info>
    <org_study_id>00099939</org_study_id>
    <nct_id>NCT04482673</nct_id>
  </id_info>
  <brief_title>Vitamin D Supplementation in the Prevention and Mitigation of COVID-19 Infection</brief_title>
  <acronym>VitD-COVID19</acronym>
  <official_title>The Role of Vitamin D in Mitigating COVID-19 Infection Severity: Focusing on Reducing Health Disparities in South Carolina</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Grassroots Health Nutrition Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>ZRT Laboratory</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of South Carolina</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate how useful vitamin D supplementation is in reducing&#xD;
      the severity of COVID-19 symptoms and the body's inflammatory and infection-fighting response&#xD;
      to COVID-19. Individuals ≥50 years of age and older who are tested for COVID-19 and negative&#xD;
      will be randomized (like flipping a coin) to either daily high dose vitamin D supplementation&#xD;
      (6000 IU vitamin D3/day) vs. standard of care. Those individuals ≥50 years of age or older&#xD;
      who test positive for COVID-19 at baseline will be randomized to bolus vitamin D (20,000&#xD;
      IU/day for 3 days) followed by high dose (6000 IU vitamin D/day) vs. standard of care for 12&#xD;
      months. All participants will receive a multivitamin containing vitamin D.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitamin D (vitD) deficiency is more prevalent among African Americans and Latinx and in the&#xD;
      elderly who have low exposure to sunlight. African Americans and nursing home residents who&#xD;
      contract SARS-CoV-2, the novel virus that first appeared in Wuhan, China, and who develop the&#xD;
      disease designated COVID-19 experience a much worse clinical outcome than other groups. Some&#xD;
      have speculated that low vitD status could exacerbate COVID-19 infection, especially if the&#xD;
      viral infection reaches the lower respiratory tract.&#xD;
&#xD;
      Sufficient vitD may help to improve the pulmonary immune response to the virus, reduce the&#xD;
      dangerous cytokine storm, and lessen surfactant dysregulation, potentially preventing or&#xD;
      ameliorating the acute syndrome. To maximize the benefits of vitD on host response to&#xD;
      SARS-CoV-2, prophylactic supplementation to ensure sufficiency before COVID-19 would be the&#xD;
      preferable public health option. Yet, vitD supplementation during acute infection may also&#xD;
      improve overall clinical outcome in some infected patients. It is a relatively inexpensive&#xD;
      therapy that has a large safety profile when given in doses of 4000-6000 international&#xD;
      units/day to adults.&#xD;
&#xD;
      To date, there is no effective cure or preventive vaccine for COVID-19. Given the risk of&#xD;
      disease and death, any intervention that reduces the morbidity and mortality from COVID-19&#xD;
      would be of immense value. We hypothesize that achieving and sustaining vitD sufficiency&#xD;
      through dietary supplementation will result in improved immune function and a decrease in&#xD;
      COVID-19 incidence and symptomatology. Importantly, this objective will address the&#xD;
      significant health disparity of vitD deficiency among black, Latina and the elderly. We&#xD;
      further hypothesize that those individuals with a circulating 25(OH)D of ≥40 ng/mL will have&#xD;
      less severe COVID-19 symptoms, particularly among higher risk populations. We will compare&#xD;
      the effectiveness of higher dose vitD vs. standard of care dosing.To test these hypotheses,&#xD;
      we propose the following Aims:&#xD;
&#xD;
        1. Focusing on prevention, this Aim will test whether achieving vitD sufficiency (as&#xD;
           defined by total circulating 25(OH)D ≥40-60 ng/mL) in individuals at risk for deficiency&#xD;
           will improve clinical outcomes in those who subsequently develop COVID-19.&#xD;
&#xD;
        2. Focusing on vitD as mitigation therapy, this Aim will evaluate the effectiveness of&#xD;
           bolus dosing followed by daily vitD supplementation in achieving the target 25(OH)D&#xD;
           range of ≥40-60 ng/mL in those individuals testing positive for COVID-19 at&#xD;
           MUSC/affiliated hospital facilities, but do not require admission to a hospital&#xD;
           (outpatient) and will examine whether achieving this target range is associated with&#xD;
           less severe COVID-19 and differences in inflammatory cytokine profiles.&#xD;
&#xD;
      In the prevention arm of this project (Aim 1), individuals at higher risk ≥50 years of age&#xD;
      who test negative for COVID-19 at MUSC/its affiliate hospitals, and agree to daily vitD&#xD;
      supplementation for a 12-month period, with vitD status measured monthly will be randomized&#xD;
      to placebo or prescribed vitD (6000 IU/day) to achieve a total circulating 25(OH)&#xD;
      concentration of ≥40-60 ng/mL. We will compare study groups regarding subsequent infection&#xD;
      with COVID-19, severity of symptoms, need and duration of hospitalization (LOS), admission to&#xD;
      the ICU, need for ventilatory support, and mortality, along with return to baseline&#xD;
      activities and/or work, as a function of age, BMI, and other recognized COVID-19 risk&#xD;
      factors. In the mitigation arm of this project (Aim 2), non-hospitalized individuals ≥50&#xD;
      years of age who test COVID-19 positive will be randomized to placebo or a bolus of oral vitD&#xD;
      (20,000 IU X 3 days) followed by 6000 IU vitD/day, and we will compare study groups on&#xD;
      measures of disease severity as in Aim 1. All participants in both Aims 1 and 2 will receive&#xD;
      a daily multivitamin (MVI) containing 800 IU VitD for the 12-month period.&#xD;
&#xD;
      Following the completion of these Aims, we will be able to answer the following questions:&#xD;
&#xD;
        1. Are individuals with vitD deficiency more likely to be diagnosed with COVID-19&#xD;
           infection?&#xD;
&#xD;
        2. Does being vitD replete make a person more likely to have asymptomatic COVID-19?&#xD;
&#xD;
        3. Does vitD sufficiency status account for why African Americans, Latina, and the elderly&#xD;
           more likely to experience complications related to COVID-19?&#xD;
&#xD;
        4. Is vitD deficiency in COVID-19 positive outpatients associated with increased severity&#xD;
           of symptoms and differences in inflammatory cytokine profiles that is mitigated by bolus&#xD;
           and then sustained vitD supplementation?&#xD;
&#xD;
      The long-term impact of these studies will influence public policy regarding more widespread&#xD;
      vitD supplementation is a means of reducing the severity of COVID-19. Given its low cost and&#xD;
      the ease with which widespread supplementation could be instituted, oral vitD supplementation&#xD;
      may represent a rapid and inexpensive means by which to reduce both the COVID-19 incidence&#xD;
      and severity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 31, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">December 31, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in total circulating 25(OH)D concentration</measure>
    <time_frame>monthly in COVID-19 negative participants through study completion for 1 year</time_frame>
    <description>metabolite of vitamin D</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in total circulating 25(OH)D concentration in COVID-19 positives</measure>
    <time_frame>baseline, 2 and 4 weeks, then months 3, 6, 9 and 12 in COVID-19 positive participants</time_frame>
    <description>metabolite of vitamin D</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in SARS-CoV-2 antibody titers</measure>
    <time_frame>every 3 months up to 12 months</time_frame>
    <description>The presence or absent of SARS-CoV-2 antibody will be measured at baseline, 3, 6, 9 and 12 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>baseline and every 3 months up to 12 months</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory symptoms</measure>
    <time_frame>daily for 2 weeks</time_frame>
    <description>COVID-19 positive participants or if COVID-19 negatives develop respiratory symptoms will complete this respiratory survey daily for 2 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Signs and symptoms of rhino/sinusitis</measure>
    <time_frame>Baseline then 3, 6, 9 and 12 months in negatives and daily for 2 weeks in positives</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NCI Dietary Intake</measure>
    <time_frame>baseline then at 6 and 12 months</time_frame>
    <description>Dietary intake assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Charlson Comorbidity survey</measure>
    <time_frame>baseline then at 6 and 12 months</time_frame>
    <description>Survey of participant health problems</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Paffenberger Physical Activity Assessment</measure>
    <time_frame>Baseline then at 6 and 12 months</time_frame>
    <description>Assessment of physical activity of each participant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived stress</measure>
    <time_frame>monthly for 1 year</time_frame>
    <description>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 &quot;never&quot; and 4 indicating &quot;very often&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pandemic stress</measure>
    <time_frame>monthly for 1 year</time_frame>
    <description>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 &quot;not at all&quot; and 5 indicating &quot;extremely,&quot; and 6 indicating &quot;decline to answer.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NEO-Personality Inventory</measure>
    <time_frame>baseline visit</time_frame>
    <description>Personality characteristics of each participant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GrassrootsHealth Monthly Health assessment</measure>
    <time_frame>baseline, 6, and 12 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">95</enrollment>
  <condition>COVID-19</condition>
  <condition>Vitamin D Deficiency</condition>
  <condition>Respiratory Viral Infection</condition>
  <arm_group>
    <arm_group_label>COVID-19 Negative Active Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>COVID-19 Negative Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants in this arm would receive placebo for 12 months. All participants will receive a multivitamin containing 800 IU vitamin D3/day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>COVID-19 Positive Active Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>COVID-19 Positive Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daily Vitamin D3</intervention_name>
    <description>6000 IU vitamin D3 daily</description>
    <arm_group_label>COVID-19 Negative Active Treatment</arm_group_label>
    <arm_group_label>COVID-19 Positive Active Treatment</arm_group_label>
    <other_name>Daily cholecalciferol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daily placebo</intervention_name>
    <description>Placebo daily</description>
    <arm_group_label>COVID-19 Negative Placebo</arm_group_label>
    <arm_group_label>COVID-19 Positive Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bolus vitamin D3</intervention_name>
    <description>Bolus 20,000 IU vitamin D3 daily for 3 days</description>
    <arm_group_label>COVID-19 Positive Active Treatment</arm_group_label>
    <other_name>Bolus cholecalciferol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bolus placebo</intervention_name>
    <description>Bolus placebo daily for 3 days</description>
    <arm_group_label>COVID-19 Positive Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Entry Criteria:&#xD;
&#xD;
        ---Adults aged 50 years of age or older who presents to MUSC or its affiliate hospitals (or&#xD;
        associated testing centers) for COVID-19 testing during the recruitment period is eligible&#xD;
        for participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hospitalization at the time of study recruitment.&#xD;
&#xD;
          -  Any individual less than 50 years of age. The reason that the participants ≥50 years&#xD;
             are being excluded from this study is because those who are ≥50 years have a higher&#xD;
             risk of being symptomatic with COVID-19 and have the potential for the greatest&#xD;
             benefit. The disease appears to manifest differently in children and its occurrence is&#xD;
             quite rare.&#xD;
&#xD;
          -  Only those patients tested for COVID-19 initially will be eligible to participate;&#xD;
             therefore, anyone wanting to participate in the trial must have had a COVID-19 test&#xD;
             prior to enrollment/participation in the study.&#xD;
&#xD;
          -  Any individual who is not capable of making independent decisions and who is&#xD;
             considered cognitively impaired.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carol L Wagner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>February 22, 2023</last_update_submitted>
  <last_update_submitted_qc>February 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of South Carolina</investigator_affiliation>
    <investigator_full_name>Carol L. Wagner, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Vitamin D Deficiency</keyword>
  <keyword>Respiratory Viral Infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Vitamin D Deficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Ergocalciferols</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Vitamins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04482673
org study id: 00099939
nct id: NCT04482673
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in total circulating 25(OH)D concentration
time frame: monthly in COVID-19 negative participants through study completion for 1 year
description: metabolite of vitamin D
measure: 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
description: metabolite of vitamin D
measure: Change in SARS-CoV-2 antibody titers
time frame: every 3 months up to 12 months
description: The presence or absent of SARS-CoV-2 antibody will be measured at baseline, 3, 6, 9 and 12 months.
measure: 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
description: 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
measure: Respiratory symptoms
time frame: daily for 2 weeks
description: COVID-19 positive participants or if COVID-19 negatives develop respiratory symptoms will complete this respiratory survey daily for 2 weeks
measure: 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
description: 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.
measure: NCI Dietary Intake
time frame: baseline then at 6 and 12 months
description: Dietary intake assessment
measure: Charlson Comorbidity survey
time frame: baseline then at 6 and 12 months
description: Survey of participant health problems
measure: Paffenberger Physical Activity Assessment
time frame: Baseline then at 6 and 12 months
description: Assessment of physical activity of each participant
measure: Perceived stress
time frame: monthly for 1 year
description: 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"
measure: Pandemic stress
time frame: monthly for 1 year
description: 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."
measure: NEO-Personality Inventory
time frame: baseline visit
description: Personality characteristics of each participant
measure: GrassrootsHealth Monthly Health assessment
time frame: baseline, 6, and 12 months
description: 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.
arm group label: COVID-19 Negative Active Treatment
arm group type: Experimental
description: 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.
arm group label: COVID-19 Negative Placebo
arm group type: Placebo Comparator
description: Participants in this arm would receive placebo for 12 months. All participants will receive a multivitamin containing 800 IU vitamin D3/day.
arm group label: COVID-19 Positive Active Treatment
arm group type: Experimental
description: 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.
arm group label: COVID-19 Positive Placebo
arm group type: Placebo Comparator
description: 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.
intervention type: Drug
intervention name: Daily Vitamin D3
description: 6000 IU vitamin D3 daily
arm group label: COVID-19 Negative Active Treatment
arm group label: COVID-19 Positive Active Treatment
other name: Daily cholecalciferol
intervention type: Drug
intervention name: Daily placebo
description: Placebo daily
arm group label: COVID-19 Negative Placebo
arm group label: COVID-19 Positive Placebo
intervention type: Drug
intervention name: Bolus vitamin D3
description: Bolus 20,000 IU vitamin D3 daily for 3 days
arm group label: COVID-19 Positive Active Treatment
other name: Bolus cholecalciferol
intervention type: Drug
intervention name: Bolus placebo
description: Bolus placebo daily for 3 days
arm group label: COVID-19 Positive Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Carol L Wagner, MD
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Medical University of South Carolina
investigator full name: Carol L. Wagner, MD
investigator title: Principal Investigator
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Virus Diseases
mesh term: Vitamin D Deficiency
mesh term: Vitamin D
mesh term: Ergocalciferols
mesh term: Cholecalciferol
mesh term: Vitamins
sharing ipd: No