<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/NCT03270709</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00094833</org_study_id>
    <nct_id>NCT03270709</nct_id>
  </id_info>
  <brief_title>Effect of High-Dose Vitamin D3 in Smokers and Non-Smokers With and Without HIV</brief_title>
  <official_title>Effect of High-Dose Vitamin D3 on Alveolar Macrophage Function, LL-37, and Oxidative Stress in Smokers and Non-Smokers With and Without HIV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Emory University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Supplementation with vitamin D improves HIV+ macrophages phagocytosis in vitro. There is&#xD;
      evidence to suggest that administering vitamin D can in fact improve immune function in&#xD;
      individuals. The study will evaluate the impact of high dose vitamin D in HIV+ smokers' and&#xD;
      HIV- smokers' in vivo. The primary goal is to improve innate immune host response to&#xD;
      infection in patients already at high risk by virtue of HIV and smoking status.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tobacco smoke suppresses the lung's ability to fight infection. Smoking is three times more&#xD;
      prevalent in the HIV+ compared to HIV- patients. Viral load was found to be significantly&#xD;
      increased in HIV+ smokers compared to HIV+ non-smokers, suggesting that smoking enhances&#xD;
      HIV-1 viral replication in macrophages, which contributes to disease progression. Vitamin D&#xD;
      deficiency has been associated with increased mortality in HIV+ persons, but there is limited&#xD;
      research on how this is impacting the health of these highest risk patients and if aggressive&#xD;
      repletion with vitamin D can improve overall health.The study team hypothesizes that vitamin&#xD;
      D administration will increase pathogen clearance and improve innate immune function.&#xD;
&#xD;
      The proposed pre and post interventional study is designed to characterize alveolar&#xD;
      macrophage function and lung immunity according to tobacco use and HIV status, and determine&#xD;
      the impact of high dose oral vitamin D3 on AM phagocytic function and innate immunity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated early due to lack of funding and the COVID-19 pandemic.&#xD;
  </why_stopped>
  <start_date type="Actual">April 11, 2018</start_date>
  <completion_date type="Actual">October 15, 2018</completion_date>
  <primary_completion_date type="Actual">October 15, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>A total of 44 subjects (11 per group, smokers and non-smokers, HIV+, HIV-) will be enrolled.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in alveolar macrophage (AM) phagocytic index between HIV+ smokers compared to HIV- non-smokers.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration.</time_frame>
    <description>A phagocytic index will be determined by challenging AM isolated from bronchoalveolar lavage (BAL) to Staph. Aureus in vitro.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration.</time_frame>
    <description>Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers will be calculated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in alveolar macrophage (AM) phagocytic index before and after vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration</time_frame>
    <description>A phagocytic index will be determined by challenging AM isolated from bronchoalveolar lavage (BAL) to Staph. Aureus in vitro.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in total and free vitamin D (25(OH) D) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration.</time_frame>
    <description>Difference in total and free 25(OH) D between HIV+ smokers compared to HIV- non-smokers will be measure by ELISA (enzyme-linked immunosorbent assay) levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in peptide LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration.</time_frame>
    <description>Difference in an antimicrobial and immunostimulating/-modulating peptide LL-37 between HIV+ smokers compared to HIV- non-smokers will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in tumor necrosis factor alpha (TNF-α) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration.</time_frame>
    <description>Difference in tumor necrosis factor alpha (TNF-α) - cytokine involved in systemic inflammation - between HIV+ smokers compared to HIV- non-smokers will be calculated .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in messenger ribonucleic acid (mRNA) expression of LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration.</time_frame>
    <description>Difference in mRNA expression of antimicrobial peptide LL-37 between HIV+ smokers compared to HIV- non-smokers will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration.</time_frame>
    <description>Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers will be measured using AM isolated from bronchoalveolar lavage (BAL) .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in total and free vitamin D (25(OH) D) before and after vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration</time_frame>
    <description>Difference in total and free vitamin D (25(OH) D) will be measure by ELISA (enzyme-linked immunosorbent assay)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in peptide LL-37 before and after vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration</time_frame>
    <description>Difference in peptide LL-37 levels will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in tumor necrosis factor alpha (TNF-α) before and after vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration</time_frame>
    <description>Difference in tumor necrosis factor alpha (TNF-α) will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in mRNA expression of LL-37 before and after vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration</time_frame>
    <description>Difference in mRNA expression of LL-37 will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in alveolar oxidative stress before and after vitamin D administration.</measure>
    <time_frame>Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration</time_frame>
    <description>Difference in alveolar oxidative stress will be measured using AM isolated from bronchoalveolar lavage (BAL) .</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>HIV/AIDS</condition>
  <condition>Vitamin D Deficiency</condition>
  <condition>Smoker Lung</condition>
  <arm_group>
    <arm_group_label>HIV+ smokers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vitamin D3 450,000 IU orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV- non-smokers</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D3 450,000 IU orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV+ non-smokers</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D3 450,000 IU orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV- smokers</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D3 450,000 IU orally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3 450,000 IU orally</intervention_name>
    <description>Study subjects will receive 2 tablets of vitamin D3 for a total of 450,000 IU by mouth.</description>
    <arm_group_label>HIV+ non-smokers</arm_group_label>
    <arm_group_label>HIV+ smokers</arm_group_label>
    <arm_group_label>HIV- non-smokers</arm_group_label>
    <arm_group_label>HIV- smokers</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects living with HIV-1 infection who have been on anti-retroviral therapy (ART)&#xD;
             for a minimum of 12 months and are followed longitudinally for their HIV healthcare;&#xD;
&#xD;
          -  Ability to give informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18 yrs old;&#xD;
&#xD;
          -  Known or possible pregnancy or breastfeeding;&#xD;
&#xD;
          -  Documented history of cirrhosis or a direct bilirubin ≥ 2.0 mg/dL;&#xD;
&#xD;
          -  Documentation of left ventricular ejection fraction &lt; 40% or myocardial infarction&#xD;
             within the past 6 months;&#xD;
&#xD;
          -  End-stage renal disease requiring dialysis or a serum creatinine ≥ 2 mg/d;&#xD;
&#xD;
          -  Spirometry with forced vital capacity (FVC) or forced expiratory volume (FEV1)&lt; 70% of&#xD;
             predicted value;&#xD;
&#xD;
          -  Bleeding disorders such as thrombocytopenia or significant gastrointestinal bleeding&#xD;
             within the past year;&#xD;
&#xD;
          -  Inability to undergo bronchoscopy safely;&#xD;
&#xD;
          -  High risk behaviors without known HIV status.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jenny E Han, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Atlanta VA Medical center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grady Health System (non-CRN), Grady Health System (CRN), Ponce Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>April 19, 2021</last_update_submitted>
  <last_update_submitted_qc>April 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Jenny Elizabeth Han</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Vitamin D3</keyword>
  <keyword>Pulmonary disease</keyword>
  <keyword>Immunosuppression</keyword>
  <keyword>HIV</keyword>
  <keyword>Smoking</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Cholecalciferol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03270709
org study id: IRB00094833
nct id: NCT03270709
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Supplementation with vitamin D improves HIV+ macrophages phagocytosis in vitro. There is
      evidence to suggest that administering vitamin D can in fact improve immune function in
      individuals. The study will evaluate the impact of high dose vitamin D in HIV+ smokers' and
      HIV- smokers' in vivo. The primary goal is to improve innate immune host response to
      infection in patients already at high risk by virtue of HIV and smoking status.
Tobacco smoke suppresses the lung's ability to fight infection. Smoking is three times more
      prevalent in the HIV+ compared to HIV- patients. Viral load was found to be significantly
      increased in HIV+ smokers compared to HIV+ non-smokers, suggesting that smoking enhances
      HIV-1 viral replication in macrophages, which contributes to disease progression. Vitamin D
      deficiency has been associated with increased mortality in HIV+ persons, but there is limited
      research on how this is impacting the health of these highest risk patients and if aggressive
      repletion with vitamin D can improve overall health.The study team hypothesizes that vitamin
      D administration will increase pathogen clearance and improve innate immune function.

      The proposed pre and post interventional study is designed to characterize alveolar
      macrophage function and lung immunity according to tobacco use and HIV status, and determine
      the impact of high dose oral vitamin D3 on AM phagocytic function and innate immunity.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: A total of 44 subjects (11 per group, smokers and non-smokers, HIV+, HIV-) will be enrolled.
primary purpose: Treatment
masking: None (Open Label)
measure: Difference in alveolar macrophage (AM) phagocytic index between HIV+ smokers compared to HIV- non-smokers.
time frame: Day 1 of the study prior to vitamin D administration.
description: A phagocytic index will be determined by challenging AM isolated from bronchoalveolar lavage (BAL) to Staph. Aureus in vitro.
measure: Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration.
description: Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers will be calculated.
measure: Difference in alveolar macrophage (AM) phagocytic index before and after vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
description: A phagocytic index will be determined by challenging AM isolated from bronchoalveolar lavage (BAL) to Staph. Aureus in vitro.
measure: Difference in total and free vitamin D (25(OH) D) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration.
description: Difference in total and free 25(OH) D between HIV+ smokers compared to HIV- non-smokers will be measure by ELISA (enzyme-linked immunosorbent assay) levels.
measure: Difference in peptide LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration.
description: Difference in an antimicrobial and immunostimulating/-modulating peptide LL-37 between HIV+ smokers compared to HIV- non-smokers will be calculated.
measure: Difference in tumor necrosis factor alpha (TNF-α) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration.
description: Difference in tumor necrosis factor alpha (TNF-α) - cytokine involved in systemic inflammation - between HIV+ smokers compared to HIV- non-smokers will be calculated .
measure: Difference in messenger ribonucleic acid (mRNA) expression of LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration.
description: Difference in mRNA expression of antimicrobial peptide LL-37 between HIV+ smokers compared to HIV- non-smokers will be calculated.
measure: Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration.
description: Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers will be measured using AM isolated from bronchoalveolar lavage (BAL) .
measure: Difference in total and free vitamin D (25(OH) D) before and after vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
description: Difference in total and free vitamin D (25(OH) D) will be measure by ELISA (enzyme-linked immunosorbent assay)
measure: Difference in peptide LL-37 before and after vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
description: Difference in peptide LL-37 levels will be calculated.
measure: Difference in tumor necrosis factor alpha (TNF-α) before and after vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
description: Difference in tumor necrosis factor alpha (TNF-α) will be calculated.
measure: Difference in mRNA expression of LL-37 before and after vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
description: Difference in mRNA expression of LL-37 will be calculated.
measure: Difference in alveolar oxidative stress before and after vitamin D administration.
time frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
description: Difference in alveolar oxidative stress will be measured using AM isolated from bronchoalveolar lavage (BAL) .
arm group label: HIV+ smokers
arm group type: Experimental
description: Vitamin D3 450,000 IU orally
arm group label: HIV- non-smokers
arm group type: Active Comparator
description: Vitamin D3 450,000 IU orally
arm group label: HIV+ non-smokers
arm group type: Active Comparator
description: Vitamin D3 450,000 IU orally
arm group label: HIV- smokers
arm group type: Active Comparator
description: Vitamin D3 450,000 IU orally
intervention type: Drug
intervention name: Vitamin D3 450,000 IU orally
description: Study subjects will receive 2 tablets of vitamin D3 for a total of 450,000 IU by mouth.
arm group label: HIV+ non-smokers
arm group label: HIV+ smokers
arm group label: HIV- non-smokers
arm group label: HIV- smokers
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jenny E Han, MD, MSc
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Jenny Elizabeth Han
investigator title: Assistant Professor
mesh term: Vitamin D Deficiency
mesh term: Vitamin D
mesh term: Cholecalciferol
sharing ipd: Undecided