<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/NCT04459247</url>
  </required_header>
  <id_info>
    <org_study_id>121/20</org_study_id>
    <nct_id>NCT04459247</nct_id>
  </id_info>
  <brief_title>Short Term, High Dose Vitamin D Supplementation for COVID-19</brief_title>
  <acronym>SHADE</acronym>
  <official_title>Short Term, High Dose Vitamin D Supplementation for COVID-19 Disease: Double Blind, Controlled, Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Postgraduate Institute of Medical Education and Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Postgraduate Institute of Medical Education and Research</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Coronavirus-2019 (COVID-19) caused by severe acute respiratory syndrome-associated&#xD;
      coronavirus-2 (SARS-CoV-2) has affected the lives of millions of individuals globally and&#xD;
      severely strained the medical community. Pre-symptomatic and asymptomatic SARS-CoV-2 positive&#xD;
      individuals far outnumber the symptomatic ones or those with severe disease. The transmission&#xD;
      potential of SARS CoV-2 is potentially greator than earlier viral outbreaks of SARS-CoV and&#xD;
      MERS-CoV. Identification of asymptomatic carriers of SARS-CoV-2 infection is paramount to&#xD;
      contain viral infection because of high transmission potential Routine measures of social&#xD;
      distancing, personal hand hygiene and limited outdoor contact activities have shown benefits&#xD;
      to limit corona virus infection. However, the role of vitamin D in SARS-CoV-2 infection is&#xD;
      not explored despite the knowledge of an immunomodulatory role and protective effect of&#xD;
      vitamin D against viral infections. It has been found that mortality from COVID-19 is more in&#xD;
      countries with vitamin D deficiency.&#xD;
&#xD;
      The role of therapeutic vitamin D supplementation in asymptomatic individuals with vitamin-D&#xD;
      deficiency and COVID-19 is not known. Immune-modulatory effect of vitamin D is likely to be&#xD;
      observed at 25(OH)D levels which are considered higher than that required for normal bone&#xD;
      metabolism.An earlier SARS-CoV-2 negativity may have significant public health benefits in&#xD;
      limiting the spread of the disease. Therefore, we hypothesise that high dose vitamin D&#xD;
      supplementation in patients with COVID-19 and vitamin D deficiency may lead to SARS-CoV-2&#xD;
      negativity in greater proportions of patients associated with decrease in serological markers&#xD;
      of inflammation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The role of therapeutic vitamin D supplementation in asymptomatic individuals with vitamin-D&#xD;
      deficiency and COVID-19 is not known. Immune-modulatory effect of vitamin D is likely to be&#xD;
      observed at 25(OH)D levels which are considered higher than that required for normal bone&#xD;
      metabolism.[6] An earlier SARS-CoV-2 negativity may have significant public health benefits&#xD;
      in limiting the spread of the disease. Therefore, we hypothesise that high dose vitamin D&#xD;
      supplementation in patients with COVID-19 and vitamin D deficiency may lead to SARS-CoV-2&#xD;
      negativity in greater proportions of patients associated with decrease in serological markers&#xD;
      of inflammation.&#xD;
&#xD;
      Methods: Consecutive individuals with SARS-CoV-2 infection who were mildly symptomatic or&#xD;
      asymptomatic with or without co-morbidities (hypertension, diabetes mellitus, chronic&#xD;
      obstructive airway disease, chronic liver disease) admitted to tertiary care hospital in&#xD;
      north India were invited for the study. A written consent was obtained from all patients&#xD;
      included in the study and protocol was approved by the Institute Ethics Committee.&#xD;
&#xD;
      Patients with vitamin D deficiency defined as 25 (OH)D level&lt;20 ng/ml were randomized to&#xD;
      receive daily 60,000IU of cholecalciferol (5 ml oral solution in nano droplet form) for seven&#xD;
      days in the &quot;intervention arm&quot; or to receive a single dose of 60,000 IU vitamin D&#xD;
      supplementation at admission in the &quot;control arm&quot;. Patients unable to take oral&#xD;
      supplementation like those requiring invasive ventilation were excluded. Subsequently,&#xD;
      25(OH)D levels were assessed at day 7 and a weekly supplementation of 60,000IU provided to&#xD;
      those with 25(OH)D &gt;50 ng/ml or continued on daily vitamin D 60,000 IU supplementation for&#xD;
      another seven days in participants with 25 (OH)D&lt;50ng/ml (day-14) in the intervention arm. No&#xD;
      vitamin D supplementation was provided in the control arm other than the initial dose at&#xD;
      hospital admission.&#xD;
&#xD;
      25 (OH)D, serum calcium, phosphorus, fibrinogen , d-dimer, C-reactive protein, procalcitonin,&#xD;
      renal and liver function tests were performed periodically up till day-21 or virus&#xD;
      negativity, whichever occurred earlier. Oro-pharyngeal swabs were obtained for SARS-CoV-2 RNA&#xD;
      detection at day-5, 7, 10, 14, 18 and 21 and detection was performed by real-time polymerase&#xD;
      chain reaction (RT-PCR), CFX-96 IVD, Bio-Rad. 25 (OH)D was analysed by&#xD;
      electrochemiluminescence immunoassay (ECLIA) (Roche Cobas E 801 Analyzer; Roche Diagnostics),&#xD;
      using the kit supplied by the same manufacturer (Elecsys Total Vitamin D, version 2.0). Serum&#xD;
      calcium (N, 8.5-10.2 mg/dl) and C-reactive protein (N, 0-5 mg/l) were processed by ECLIA&#xD;
      method using Roche Cobas 8000, Roche Diagnostics. D dimer (N, 0-240 ng/ml) &amp; fibrinogen (N,&#xD;
      2-4g/l) were analyzed using Stago Compact/ Stago STA R model, Diagnostica Stago, Inc, USA&#xD;
      respectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Actual">April 10, 2021</completion_date>
  <primary_completion_date type="Actual">March 30, 2021</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Virus negativity</measure>
    <time_frame>21 days</time_frame>
    <description>SARS-CoV-2 RNA negative</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Inflammatory Marker</measure>
    <time_frame>21 days</time_frame>
    <description>Change in fibrinogenLevels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory Marker 2</measure>
    <time_frame>21 days</time_frame>
    <description>Change in D-Dimer Levels</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vitamin D high dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No Vitamin D supplementation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vit D</intervention_name>
    <description>Oral liquid formulation of 60000 IU</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  SARS-CoV-2 RNA positive Asymptomatic individuals&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled Diabetes Uncontrolled Hypertension Chronic Liver Disease Chronic&#xD;
             obstructive Pulmonary disease Requiring Invasive Ventilation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Deptt of Endocrinology</name>
      <address>
        <city>Chandigarh</city>
        <zip>160012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>October 30, 2021</last_update_submitted>
  <last_update_submitted_qc>October 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
    <investigator_full_name>Ashu Rastogi</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <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/NCT04459247
org study id: 121/20
nct id: NCT04459247
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Coronavirus-2019 (COVID-19) caused by severe acute respiratory syndrome-associated
      coronavirus-2 (SARS-CoV-2) has affected the lives of millions of individuals globally and
      severely strained the medical community. Pre-symptomatic and asymptomatic SARS-CoV-2 positive
      individuals far outnumber the symptomatic ones or those with severe disease. The transmission
      potential of SARS CoV-2 is potentially greator than earlier viral outbreaks of SARS-CoV and
      MERS-CoV. Identification of asymptomatic carriers of SARS-CoV-2 infection is paramount to
      contain viral infection because of high transmission potential Routine measures of social
      distancing, personal hand hygiene and limited outdoor contact activities have shown benefits
      to limit corona virus infection. However, the role of vitamin D in SARS-CoV-2 infection is
      not explored despite the knowledge of an immunomodulatory role and protective effect of
      vitamin D against viral infections. It has been found that mortality from COVID-19 is more in
      countries with vitamin D deficiency.

      The role of therapeutic vitamin D supplementation in asymptomatic individuals with vitamin-D
      deficiency and COVID-19 is not known. Immune-modulatory effect of vitamin D is likely to be
      observed at 25(OH)D levels which are considered higher than that required for normal bone
      metabolism.An earlier SARS-CoV-2 negativity may have significant public health benefits in
      limiting the spread of the disease. Therefore, we hypothesise that high dose vitamin D
      supplementation in patients with COVID-19 and vitamin D deficiency may lead to SARS-CoV-2
      negativity in greater proportions of patients associated with decrease in serological markers
      of inflammation.
The role of therapeutic vitamin D supplementation in asymptomatic individuals with vitamin-D
      deficiency and COVID-19 is not known. Immune-modulatory effect of vitamin D is likely to be
      observed at 25(OH)D levels which are considered higher than that required for normal bone
      metabolism.[6] An earlier SARS-CoV-2 negativity may have significant public health benefits
      in limiting the spread of the disease. Therefore, we hypothesise that high dose vitamin D
      supplementation in patients with COVID-19 and vitamin D deficiency may lead to SARS-CoV-2
      negativity in greater proportions of patients associated with decrease in serological markers
      of inflammation.

      Methods: Consecutive individuals with SARS-CoV-2 infection who were mildly symptomatic or
      asymptomatic with or without co-morbidities (hypertension, diabetes mellitus, chronic
      obstructive airway disease, chronic liver disease) admitted to tertiary care hospital in
      north India were invited for the study. A written consent was obtained from all patients
      included in the study and protocol was approved by the Institute Ethics Committee.

      Patients with vitamin D deficiency defined as 25 (OH)D level<20 ng/ml were randomized to
      receive daily 60,000IU of cholecalciferol (5 ml oral solution in nano droplet form) for seven
      days in the "intervention arm" or to receive a single dose of 60,000 IU vitamin D
      supplementation at admission in the "control arm". Patients unable to take oral
      supplementation like those requiring invasive ventilation were excluded. Subsequently,
      25(OH)D levels were assessed at day 7 and a weekly supplementation of 60,000IU provided to
      those with 25(OH)D >50 ng/ml or continued on daily vitamin D 60,000 IU supplementation for
      another seven days in participants with 25 (OH)D<50ng/ml (day-14) in the intervention arm. No
      vitamin D supplementation was provided in the control arm other than the initial dose at
      hospital admission.

      25 (OH)D, serum calcium, phosphorus, fibrinogen , d-dimer, C-reactive protein, procalcitonin,
      renal and liver function tests were performed periodically up till day-21 or virus
      negativity, whichever occurred earlier. Oro-pharyngeal swabs were obtained for SARS-CoV-2 RNA
      detection at day-5, 7, 10, 14, 18 and 21 and detection was performed by real-time polymerase
      chain reaction (RT-PCR), CFX-96 IVD, Bio-Rad. 25 (OH)D was analysed by
      electrochemiluminescence immunoassay (ECLIA) (Roche Cobas E 801 Analyzer; Roche Diagnostics),
      using the kit supplied by the same manufacturer (Elecsys Total Vitamin D, version 2.0). Serum
      calcium (N, 8.5-10.2 mg/dl) and C-reactive protein (N, 0-5 mg/l) were processed by ECLIA
      method using Roche Cobas 8000, Roche Diagnostics. D dimer (N, 0-240 ng/ml) & fibrinogen (N,
      2-4g/l) were analyzed using Stago Compact/ Stago STA R model, Diagnostica Stago, Inc, USA
      respectively.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Virus negativity
time frame: 21 days
description: SARS-CoV-2 RNA negative
measure: Inflammatory Marker
time frame: 21 days
description: Change in fibrinogenLevels
measure: Inflammatory Marker 2
time frame: 21 days
description: Change in D-Dimer Levels
arm group label: Intervention
arm group type: Experimental
description: Vitamin D high dose
arm group label: Control arm
arm group type: No Intervention
description: No Vitamin D supplementation
intervention type: Drug
intervention name: Vit D
description: Oral liquid formulation of 60000 IU
arm group label: Intervention
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: India
responsible party type: Principal Investigator
investigator affiliation: Postgraduate Institute of Medical Education and Research
investigator full name: Ashu Rastogi
investigator title: Assistant Professor
sharing ipd: No