<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/NCT02186535</url>
  </required_header>
  <id_info>
    <org_study_id>A14-131</org_study_id>
    <nct_id>NCT02186535</nct_id>
  </id_info>
  <brief_title>The Role of Vitamin D in Female Reproductive Tract Immunity</brief_title>
  <official_title>The Role of Vitamin D in Female Reproductive Tract Immunity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CONRAD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CONRAD</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the impact of approximately 8 weeks of Vitamin D&#xD;
      (VitD) and calcium supplementation, using daily versus weekly supplementation regimens, on&#xD;
      female reproductive tract immunity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This outpatient open label study will assess the impact of 8 weeks of daily versus weekly&#xD;
      VitD and calcium supplementation on measures of cervicovaginal (CV) innate immune function,&#xD;
      including antimicrobial and proinflammatory gene expression, Toll-like receptor&#xD;
      (TLR)-mediated responses, immunohistochemical (IHC) analysis of immune cell markers, and&#xD;
      microbiota in premenopausal women with insufficient serum VitD levels at baseline.&#xD;
&#xD;
      Women will be seen in 3 study visits and will be contacted by one scheduled follow-up&#xD;
      telephone call after their final study visit. Volunteers will be consented at Visit 1 and&#xD;
      undergo procedures to confirm they are eligible to continue in the study.&#xD;
&#xD;
      Once it has been confirmed that the participant meets all of the inclusion criteria and none&#xD;
      of the exclusion criteria, baseline blood and genital samples will be taken in the luteal&#xD;
      phase at Visit 2. The participant will then be given their first dose of VitD 4000 IU daily&#xD;
      or 50,000 IU weekly in capsule form, which they will then administer for 8 weeks.&#xD;
      Participants will also administer 1000 mg of calcium daily. Participants will return upon&#xD;
      completion of supplementation for repeat of blood and genital samples (Visit 3).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 1</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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vitamin D concentrations in serum and vaginal secretions</measure>
    <time_frame>over 8 weeks of use</time_frame>
    <description>Assess the impact of daily versus weekly Vitamin D and calcium supplementation regimens on Vitamin D concentrations in serum and on soluble markers innate mucosal immunity and inflammatory response in cervicovaginal secretions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of Gene Expression</measure>
    <time_frame>over 8 weeks of use</time_frame>
    <description>Assess gene expression of epithelial factors associated with innate immune response in CV tissues before and after VitD and calcium supplementation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of immune cell activation and phenotype by IHC in CV tissues</measure>
    <time_frame>over 8 weeks of use</time_frame>
    <description>Assess immune cell activation and phenotype by IHC in CV tissues before and after VitD and calcium supplementation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Vitamin D Deficiency</condition>
  <arm_group>
    <arm_group_label>Daily dosing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Daily oral capsule of Vitamin D in 4000 IU/day with daily oral capsules of 1000mg of calcium</description>
  </arm_group>
  <arm_group>
    <arm_group_label>weekly dosing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Oral capsule Vitamin D 50,000 IU/week with a oral capsule of 1000mg of calcium, daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D and Calcium</intervention_name>
    <arm_group_label>Daily dosing</arm_group_label>
    <arm_group_label>weekly dosing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Serum 25(OH)D ≤ 25ng/mL (62 nmol/L)&#xD;
&#xD;
          -  In good health, as evidenced by history and procedures at screening visits without any&#xD;
             clinically significant systemic disease.&#xD;
&#xD;
          -  Not at risk of an STI, meaning: In a monogamous heterosexual or same sex relationship&#xD;
             with a partner who is not known to be HIV positive and has no known risks for STIs, or&#xD;
             Sexually abstinent&#xD;
&#xD;
          -  Willing and able to comply with study procedures&#xD;
&#xD;
          -  21 to 50 years of age&#xD;
&#xD;
          -  Not at risk for pregnancy, meaning: Protected from pregnancy due to surgical&#xD;
             sterilization of participant and or her sexual partner, Consistent condom use, In a&#xD;
             same sex relationship or, Abstinent from sexual activity and planning to remain&#xD;
             abstinent for the duration of the study&#xD;
&#xD;
          -  Regular menstrual cycles (every 21 - 35 days) for the past two cycles, per participant&#xD;
             report&#xD;
&#xD;
          -  Willing to use sunscreen of SPF15 or higher when exposed to the sun for at least 15&#xD;
             minutes, and to avoid use of non-study Vitamin D, calcium, and multivitamin&#xD;
             supplementation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A clinically significant history of an abnormal Pap test (by written report) in the&#xD;
             past year that has not been evaluated and/or treated, if indicated, according to&#xD;
             standard guidelines&#xD;
&#xD;
          -  Surgery or biopsy of the vagina or cervix within 14 days&#xD;
&#xD;
          -  Current STI or lower genital tract infection including HIV-1, Chlamydia trachomatis&#xD;
             (CT), Trichomonas vaginalis (TV), Neisseria Gonorrhoeae (NG), Hepatitis B, yeast&#xD;
             vaginitis or bacterial vaginosis (BV) (by Nugent score of 7 - 10); this does not&#xD;
             include asymptomatic HSV or human papilloma virus (HPV)&#xD;
&#xD;
          -  Current presence of vulvar, anal and/or vaginal genital warts&#xD;
&#xD;
          -  Current tobacco use of any amount&#xD;
&#xD;
          -  Body Mass Index (BMI) of ≥ 35 kg/m2&#xD;
&#xD;
          -  History of sensitivity/allergy to any component of the study product, topical&#xD;
             anesthetic, or allergy to silver nitrate and/or Monsel's solution&#xD;
&#xD;
          -  Known bleeding disorder that could lead to prolonged or continuous bleeding with&#xD;
             biopsy, or taking anticoagulant drugs&#xD;
&#xD;
          -  Grade 2 or higher laboratory abnormality, per the August 2009 update of the DAIDS&#xD;
             Table for Grading the Severity of Adverse Events&#xD;
&#xD;
          -  Systemic use in the last two weeks or anticipated use during the study of any of the&#xD;
             following: corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs),&#xD;
             antibiotics, anticoagulants or other drugs known to prolong bleeding and/or clotting,&#xD;
             antifungals, antivirals (e.g., acyclovir or valacyclovir) or antiretrovirals (e.g.,&#xD;
             Viread). Note: Participants should avoid NSAIDS except for treatment of dysmenorrhea&#xD;
             during menses. Participants may use acetaminophen on an as-needed but not daily basis&#xD;
             during the study.&#xD;
&#xD;
          -  Known risk factors for hypercalcemia (e.g. malignancy or granulomatous disease) or&#xD;
             malabsorption syndromes (e.g. celiac disease, radiation enteritis, active inflammatory&#xD;
             bowel disease).&#xD;
&#xD;
          -  Other conditions that, in the opinion of the investigator, would constitute&#xD;
             contraindications to participation in the study or would compromise the ability to&#xD;
             comply with study protocols, such as any major chronic illness including but not&#xD;
             limited to cancer, serious autoimmune disease, metabolic disorders or a major&#xD;
             psychiatric disorder (e.g., schizophrenia)&#xD;
&#xD;
          -  Current participation in any other drug or device study, or any study which, in the&#xD;
             opinion of the investigator, would jeopardize interpretation of results of this study&#xD;
&#xD;
          -  Use of depot medroxyprogesterone acetate (DMPA) in last six months&#xD;
&#xD;
          -  Use of any other hormonal contraceptive method (oral, transdermal, transvaginal,&#xD;
             implant, or intrauterine device) without 2 subsequent, normal menses since stopping&#xD;
             hormonal contraceptives&#xD;
&#xD;
          -  Current use of copper IUD&#xD;
&#xD;
          -  Currently pregnant or pregnancy within the past 3 months&#xD;
&#xD;
          -  Currently breastfeeding or having breastfed an infant in the last two months&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrea Thurman, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>CONRAD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Eastern Virginia Medical School CONRAD Clinical Research Center</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>July 1, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>January 7, 2016</last_update_submitted>
  <last_update_submitted_qc>January 7, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Calcium</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02186535
org study id: A14-131
nct id: NCT02186535
lead sponsor: 
The purpose of this study is to assess the impact of approximately 8 weeks of Vitamin D
      (VitD) and calcium supplementation, using daily versus weekly supplementation regimens, on
      female reproductive tract immunity.
This outpatient open label study will assess the impact of 8 weeks of daily versus weekly
      VitD and calcium supplementation on measures of cervicovaginal (CV) innate immune function,
      including antimicrobial and proinflammatory gene expression, Toll-like receptor
      (TLR)-mediated responses, immunohistochemical (IHC) analysis of immune cell markers, and
      microbiota in premenopausal women with insufficient serum VitD levels at baseline.

      Women will be seen in 3 study visits and will be contacted by one scheduled follow-up
      telephone call after their final study visit. Volunteers will be consented at Visit 1 and
      undergo procedures to confirm they are eligible to continue in the study.

      Once it has been confirmed that the participant meets all of the inclusion criteria and none
      of the exclusion criteria, baseline blood and genital samples will be taken in the luteal
      phase at Visit 2. The participant will then be given their first dose of VitD 4000 IU daily
      or 50,000 IU weekly in capsule form, which they will then administer for 8 weeks.
      Participants will also administer 1000 mg of calcium daily. Participants will return upon
      completion of supplementation for repeat of blood and genital samples (Visit 3).
allocation: Randomized
intervention model: Parallel Assignment
masking: None (Open Label)
measure: Vitamin D concentrations in serum and vaginal secretions
time frame: over 8 weeks of use
description: Assess the impact of daily versus weekly Vitamin D and calcium supplementation regimens on Vitamin D concentrations in serum and on soluble markers innate mucosal immunity and inflammatory response in cervicovaginal secretions.
measure: Assessment of Gene Expression
time frame: over 8 weeks of use
description: Assess gene expression of epithelial factors associated with innate immune response in CV tissues before and after VitD and calcium supplementation.
measure: Assessment of immune cell activation and phenotype by IHC in CV tissues
time frame: over 8 weeks of use
description: Assess immune cell activation and phenotype by IHC in CV tissues before and after VitD and calcium supplementation.
arm group label: Daily dosing
arm group type: Other
description: Daily oral capsule of Vitamin D in 4000 IU/day with daily oral capsules of 1000mg of calcium
arm group label: weekly dosing
arm group type: Other
description: Oral capsule Vitamin D 50,000 IU/week with a oral capsule of 1000mg of calcium, daily
intervention type: Dietary Supplement
intervention name: Vitamin D and Calcium
arm group label: Daily dosing
arm group label: weekly dosing
criteria: 
gender: Female
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Andrea Thurman, M.D.
role: Principal Investigator
affiliation: CONRAD
facility: 
country: United States
responsible party type: Sponsor
mesh term: Vitamin D Deficiency
mesh term: Vitamin D
mesh term: Calcium