<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/NCT04443387</url>
  </required_header>
  <id_info>
    <org_study_id>MRC-04/2012_06</org_study_id>
    <nct_id>NCT04443387</nct_id>
  </id_info>
  <brief_title>Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients</brief_title>
  <acronym>VitaminD</acronym>
  <official_title>Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dubai Health Authority</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>McGill University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dubai Health Authority</source>
  <oversight_info>
    <has_dmc>No</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>
      Vitamin D (VitD) deficiency is a significant public health concern in many areas around the&#xD;
      globe which has been associated with many immune-mediated diseases, including asthma. Severe&#xD;
      asthma has been linked with a decreased glucocorticoid receptors (GR) ratio (GR-α/ GR-β&#xD;
      ratio), indicating steroid hyporesponsiveness. Using combined in silico and in vivo&#xD;
      approaches, aimed to explore the immunomodulatory effect of VitD on asthmatic patients&#xD;
      diagnosed with hypovitaminosis D.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitamin D (VitD) deficiency is a significant public health concern in many areas around the&#xD;
      globe which has been associated with many immune-mediated diseases, including asthma. Severe&#xD;
      asthma has been linked with a decreased glucocorticoid receptors (GR) ratio (GR-α/ GR-β&#xD;
      ratio), indicating steroid hyporesponsiveness. Using combined in silico and in vivo&#xD;
      approaches, the investigators aimed to explore the immunomodulatory effect of VitD on&#xD;
      asthmatic patients diagnosed with hypovitaminosis D. Methods: In silico tools were used to&#xD;
      identify the regulatory effect of VitD supplementation on GR genes. The investigators&#xD;
      measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult&#xD;
      asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover,&#xD;
      the blood levels of inflammatory cytokines associated with asthma severity were determined.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2012</start_date>
  <completion_date type="Actual">December 31, 2014</completion_date>
  <primary_completion_date type="Actual">April 30, 2014</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>
    <intervention_model_description>double blinded randomized study</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The top Vitamin D regulated pathways in response to Steroids by using Comparative Toxicogenomics Database from thousands of experiments.</measure>
    <time_frame>8 weeks</time_frame>
    <description>identify VitD targeted enriched pathways, we analyzed Comparative Toxicogenomics .Enriched Ontology Clustering for the identified genes was performed using the Metascape (a web-based tool used for comprehensive gene list annotation and analysis resource)Database from thousands of experiments.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Asthma Severity effects on VDR and steroid receptors genes by inalyzing expression profile of publicly available datasets (GSE69683) which has a large number of participants and detailed clinical information.</measure>
    <time_frame>8 weeks</time_frame>
    <description>analyze the expression profile of publicly available datasets (GSE69683) which has a large number of participants and detailed clinical information.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Examine the up-regulation of GR-α receptor by using supplementation of vitamin D on 45 vitamin D deficient asthmatics</measure>
    <time_frame>8 weeks</time_frame>
    <description>by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics.Standard statistical t-tests and one-way ANOVA were performed to test for statistical significance between data groups using GraphPad Prism 8 (GraphPad, San Diego, CA, USA). p &lt; 0.05 was considered significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of IL-17 and IL-4 cytokines in asthmatic patients while using Vitamin D supplementation by using ELISA assay</measure>
    <time_frame>8 weeks</time_frame>
    <description>by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics. Using qRT-PCR expression of the cytokines</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of IL-17 and IL-4 cytokines in asthmatic patients while using Vitamin D supplementation by using ELISA assay</measure>
    <time_frame>8 weeks</time_frame>
    <description>by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics.using Bioplex multiplex immunoassay (BioRad, CA,USA) was used to assess the protein expression of the cytokines and by measuring fold change.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Effect of Drug</condition>
  <arm_group>
    <arm_group_label>Asthmatic low vitamin D on treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>asthmatic patient low vitamin D level received treatment for Vitamin D 50000IU weekly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Asthmatic low vitamin D on placepo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>asthmatic patient low vitamin D level received placepo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D</intervention_name>
    <description>A double-blinded, randomized, placebo-controlled study of VitD supplementation on 45 asthmatics with VitD deficiency was performed. Moderate to severe asthmatics between 18 and 65 years of age who had clinician-diagnosed asthma with 25-hydroxyvitamin D3 (25 D3) level less than 20ng/mL at the screening visit were recruited at the Rashid Hospital, Dubai, U.A.E., and the Zayed Military Hospital, Abu Dhabi, U.A.E. Subjects were excluded if they had used any previous VitD supplementation, had any other respiratory diseases or co-morbid conditions or were smokers. According to the American Academy of Family Physicians guidelines, participants received 50, 000 IU of VitD orally or placebo weekly over 8 weeks. Subjects were blinded to treatment and allocated to receive a VitD dose or placebo by the randomization schedule.</description>
    <arm_group_label>Asthmatic low vitamin D on treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A double-blinded, randomized, placebo-controlled study of VitD supplementation on 45 asthmatics with VitD deficiency was performed. Moderate to severe asthmatics between 18 and 65 years of age who had clinician-diagnosed asthma with 25-hydroxyvitamin D3 (25 D3) level less than 20ng/mL at the screening visit were recruited at the Rashid Hospital, Dubai, U.A.E., and the Zayed Military Hospital, Abu Dhabi, U.A.E. Subjects were excluded if they had used any previous VitD supplementation, had any other respiratory diseases or co-morbid conditions or were smokers. According to the American Academy of Family Physicians guidelines, participants received 50, 000 IU of VitD orally or placebo weekly over 8 weeks. Subjects were blinded to treatment and allocated to receive a VitD dose or placebo by the randomization schedule.</description>
    <arm_group_label>Asthmatic low vitamin D on placepo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of asthma&#xD;
&#xD;
          -  age group between 18 and 65 years&#xD;
&#xD;
          -  low level of 25-hydroxyvitamin D3 (25 D3) level less than 20ng/mL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  smoker patients&#xD;
&#xD;
          -  less than 18 years old&#xD;
&#xD;
          -  patient on Vitamin D supplementation already&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 19, 2020</last_update_submitted>
  <last_update_submitted_qc>June 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dubai Health Authority</investigator_affiliation>
    <investigator_full_name>Bassam Mahboub</investigator_full_name>
    <investigator_title>Consultant and Head of department (pulmonary unit)</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 16, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT04443387/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04443387
org study id: MRC-04/2012_06
nct id: NCT04443387
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Vitamin D (VitD) deficiency is a significant public health concern in many areas around the
      globe which has been associated with many immune-mediated diseases, including asthma. Severe
      asthma has been linked with a decreased glucocorticoid receptors (GR) ratio (GR-α/ GR-β
      ratio), indicating steroid hyporesponsiveness. Using combined in silico and in vivo
      approaches, aimed to explore the immunomodulatory effect of VitD on asthmatic patients
      diagnosed with hypovitaminosis D.
Vitamin D (VitD) deficiency is a significant public health concern in many areas around the
      globe which has been associated with many immune-mediated diseases, including asthma. Severe
      asthma has been linked with a decreased glucocorticoid receptors (GR) ratio (GR-α/ GR-β
      ratio), indicating steroid hyporesponsiveness. Using combined in silico and in vivo
      approaches, the investigators aimed to explore the immunomodulatory effect of VitD on
      asthmatic patients diagnosed with hypovitaminosis D. Methods: In silico tools were used to
      identify the regulatory effect of VitD supplementation on GR genes. The investigators
      measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult
      asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover,
      the blood levels of inflammatory cytokines associated with asthma severity were determined.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: double blinded randomized study
primary purpose: Basic Science
masking: Single (Investigator)
measure: The top Vitamin D regulated pathways in response to Steroids by using Comparative Toxicogenomics Database from thousands of experiments.
time frame: 8 weeks
description: identify VitD targeted enriched pathways, we analyzed Comparative Toxicogenomics .Enriched Ontology Clustering for the identified genes was performed using the Metascape (a web-based tool used for comprehensive gene list annotation and analysis resource)Database from thousands of experiments.
measure: Asthma Severity effects on VDR and steroid receptors genes by inalyzing expression profile of publicly available datasets (GSE69683) which has a large number of participants and detailed clinical information.
time frame: 8 weeks
description: analyze the expression profile of publicly available datasets (GSE69683) which has a large number of participants and detailed clinical information.
measure: Examine the up-regulation of GR-α receptor by using supplementation of vitamin D on 45 vitamin D deficient asthmatics
time frame: 8 weeks
description: by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics.Standard statistical t-tests and one-way ANOVA were performed to test for statistical significance between data groups using GraphPad Prism 8 (GraphPad, San Diego, CA, USA). p < 0.05 was considered significant.
measure: Effects of IL-17 and IL-4 cytokines in asthmatic patients while using Vitamin D supplementation by using ELISA assay
time frame: 8 weeks
description: by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics. Using qRT-PCR expression of the cytokines
measure: Effects of IL-17 and IL-4 cytokines in asthmatic patients while using Vitamin D supplementation by using ELISA assay
time frame: 8 weeks
description: by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics.using Bioplex multiplex immunoassay (BioRad, CA,USA) was used to assess the protein expression of the cytokines and by measuring fold change.
arm group label: Asthmatic low vitamin D on treatment
arm group type: Active Comparator
description: asthmatic patient low vitamin D level received treatment for Vitamin D 50000IU weekly
arm group label: Asthmatic low vitamin D on placepo
arm group type: Placebo Comparator
description: asthmatic patient low vitamin D level received placepo
intervention type: Drug
intervention name: Vitamin D
description: A double-blinded, randomized, placebo-controlled study of VitD supplementation on 45 asthmatics with VitD deficiency was performed. Moderate to severe asthmatics between 18 and 65 years of age who had clinician-diagnosed asthma with 25-hydroxyvitamin D3 (25 D3) level less than 20ng/mL at the screening visit were recruited at the Rashid Hospital, Dubai, U.A.E., and the Zayed Military Hospital, Abu Dhabi, U.A.E. Subjects were excluded if they had used any previous VitD supplementation, had any other respiratory diseases or co-morbid conditions or were smokers. According to the American Academy of Family Physicians guidelines, participants received 50, 000 IU of VitD orally or placebo weekly over 8 weeks. Subjects were blinded to treatment and allocated to receive a VitD dose or placebo by the randomization schedule.
arm group label: Asthmatic low vitamin D on treatment
intervention type: Other
intervention name: Placebo
description: A double-blinded, randomized, placebo-controlled study of VitD supplementation on 45 asthmatics with VitD deficiency was performed. Moderate to severe asthmatics between 18 and 65 years of age who had clinician-diagnosed asthma with 25-hydroxyvitamin D3 (25 D3) level less than 20ng/mL at the screening visit were recruited at the Rashid Hospital, Dubai, U.A.E., and the Zayed Military Hospital, Abu Dhabi, U.A.E. Subjects were excluded if they had used any previous VitD supplementation, had any other respiratory diseases or co-morbid conditions or were smokers. According to the American Academy of Family Physicians guidelines, participants received 50, 000 IU of VitD orally or placebo weekly over 8 weeks. Subjects were blinded to treatment and allocated to receive a VitD dose or placebo by the randomization schedule.
arm group label: Asthmatic low vitamin D on placepo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Dubai Health Authority
investigator full name: Bassam Mahboub
investigator title: Consultant and Head of department (pulmonary unit)
mesh term: Asthma
mesh term: Vitamin D
provided document: 