<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/NCT01721915</url>
  </required_header>
  <id_info>
    <org_study_id>VitDPCOS1.0</org_study_id>
    <secondary_id>KLI 274</secondary_id>
    <nct_id>NCT01721915</nct_id>
  </id_info>
  <brief_title>Vitamin D Treatment, Pharmacogenetics and Glucose Metabolism</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Effects of Vitamin D Supplementation on Metabolic and Fertility Parameters in PCOS Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Austrian Science Fund (FWF)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of Graz</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Polycystic ovary syndrome (PCOS) is as common as 5-10% of all women in Austria.&#xD;
      PCOS women frequently present with metabolic disturbances, hyperandrogenism and infertility.&#xD;
      New therapy concepts are warranted. In our recent pilot study, vitamin D (vitD)&#xD;
      supplementation significantly improved glucose metabolism and fertility. However, the&#xD;
      efficacy of vitD administration shows individual variability indicating endogenous influences&#xD;
      on pharmacological effects.&#xD;
&#xD;
      A recent genome-wide association study reported three loci (DHCR7, CYP2R1, and GC) associated&#xD;
      with vitD insufficiency. Moreover, vitD receptor (VDR) gene variants have already been known&#xD;
      to be associated with insulin resistance.&#xD;
&#xD;
      Aim: To test the hypothesis that vitD is efficient in changing metabolic parameters in PCOS&#xD;
      and non-PCOS women longitudinally and to generate data on pharmacogenetic effects of vitD&#xD;
      related genetic determinants adjusted for environmental factors.&#xD;
&#xD;
      Primary outcome: Change from baseline in AUCgluc after vitD treatment. Secondary outcome: To&#xD;
      generate the hypothesis that changes in metabolic and endocrine parameters following vitD&#xD;
      treatment are associated with vitD related gene variants.&#xD;
&#xD;
      Methods: 150 PCOS women with 25-hydroxyvitamin D (cholecalciferol, [25(OH)D]) levels &lt;30&#xD;
      ng/ml will be treated with vitD (20,000 IU/wk) or placebo in a 2:1 randomized controlled&#xD;
      trial over 24 weeks and investigated for metabolic and endocrine parameters as well as vitD&#xD;
      related genetic variants. In addition, 150 non-PCOS women with 25(OH)D &lt;30 ng/ml will be&#xD;
      treated with vitD (20,000 IU/wk) or placebo in a 2:1 randomized controlled trial over 24&#xD;
      weeks and investigated for metabolic and endocrine parameters as well as vitD related genetic&#xD;
      variants. The response to vitD supplementation in both groups will be analysed according to&#xD;
      genotype profiles.&#xD;
&#xD;
      Significance: VitD might be a new therapeutic option without major side effects for PCOS&#xD;
      patients. Exploring specific loci for pharmacogenetic vitD actions would open a new window&#xD;
      for therapy modulation in PCOS and other metabolic diseases.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">October 12, 2017</completion_date>
  <primary_completion_date type="Actual">October 12, 2017</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCgluc</measure>
    <time_frame>Change from Baseline in AUC gluc at 24 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR)</measure>
    <time_frame>Change from Baseline in insulin resistance at 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid levels (total cholesterol)</measure>
    <time_frame>Change from Baseline in total cholesterol at 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1c</measure>
    <time_frame>Change from Baseline in HbA1c at 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Testosterone</measure>
    <time_frame>Change from Baseline in testosterone at 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Menstrual frequency</measure>
    <time_frame>Change from Baseline in menstrual frequency at 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin sensitivity assessed by Quantitative Insulin-sensitivity Check Index (QUICKI)</measure>
    <time_frame>Change from baseline in QUICKI at 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Free testosterone (FT)</measure>
    <time_frame>Change from Baseline in FT at 4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Triglycerides</measure>
    <time_frame>Change from Baseline in triglycerides at 24 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">330</enrollment>
  <condition>Polycystic Ovary Syndrome</condition>
  <condition>Healthy</condition>
  <condition>Vitamin D Deficiency</condition>
  <arm_group>
    <arm_group_label>Vitamin D supplementation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The treatment group will receive an oral dose of 20,000 IU vitD weekly (equivalent to 2857 IU/day) as oily drops (Oleovit D3-drops; producer: Fresenius Kabi Austria GmbH, Linz)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>the placebo group will receive oily drops without vitD</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D supplementation</intervention_name>
    <description>The treatment group will receive an oral dose of 20,000 IU vitD weekly (equivalent to 2857 IU/day) as oily drops (Oleovit D3-drops; producer: Fresenius Kabi Austria GmbH, Linz)</description>
    <arm_group_label>Vitamin D supplementation</arm_group_label>
    <other_name>A11CC05 Colecalciferol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        PCOS women:&#xD;
&#xD;
          -  25(OH)D levels below 30 ng/ml (measured at the baseline visit)&#xD;
&#xD;
          -  Polycystic ovary syndrome defined by the Androgen Excess Society (AES) criteria&#xD;
&#xD;
          -  Female, age of ≥ 18 and &lt;45 years&#xD;
&#xD;
          -  BMI status: 75 PCOS women with BMI ≤25 kg/m² and 75 PCOS women with BMI&gt;25 kg/m²&#xD;
&#xD;
          -  Written informed consent before study entry&#xD;
&#xD;
        Control women:&#xD;
&#xD;
          -  25(OH)D levels below 30 ng/ml (measured at the baseline visit)&#xD;
&#xD;
          -  Female, age of ≥ 18 and &lt;45 years&#xD;
&#xD;
          -  BMI status: 75 nonPCOS women with BMI ≤25 kg/m² and 75 nonPCOS women with BMI&gt;25 kg/m²&#xD;
&#xD;
          -  Written informed consent before study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        PCOS women:&#xD;
&#xD;
          -  Hypercalcemia defined as a serum calcium &gt; 2,7 mmol/L&#xD;
&#xD;
          -  Pregnancy or lactating women&#xD;
&#xD;
          -  Disorders associated with androgen excess and/or menstrual irregularities apart from&#xD;
             PCOS (thyroid dysfunction, hyperprolactinemia, adrenal hyperplasia, androgen secreting&#xD;
             tumors)&#xD;
&#xD;
          -  Prevalent type 2 diabetes&#xD;
&#xD;
          -  Regular intake of vitD supplements at any time before study entry&#xD;
&#xD;
          -  Intake of medication influencing metabolic or endocrine parameters (insulin&#xD;
             sensitizers, oral contraceptives, …) in the last 3 months before study entry&#xD;
&#xD;
        Control women:&#xD;
&#xD;
          -  Hypercalcemia defined as a serum calcium &gt; 2,7 mmol/L&#xD;
&#xD;
          -  Established PCOS or any of the AES criteria 29 (hyperandrogenism (clinical and/or&#xD;
             biochemical), oligo- or anovulation, or polycystic ovaries on ultrasound)&#xD;
&#xD;
          -  Disorders associated with androgen excess and/or menstrual irregularities apart from&#xD;
             PCOS (thyroid dysfunction, hyperprolactinemia, adrenal hyperplasia, androgen secreting&#xD;
             tumors)&#xD;
&#xD;
          -  Prevalent type 2 diabetes&#xD;
&#xD;
          -  Pregnancy or lactating women&#xD;
&#xD;
          -  Regular intake of vitD supplements at any time before study entry&#xD;
&#xD;
          -  Intake of medication influencing metabolic or endocrine parameters (insulin&#xD;
             sensitizers, oral contraceptives, …) in the last 3 months before study entry&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>44 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elisabeth Lerchbaum, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Graz</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Metabolism</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>October 31, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>March 17, 2018</last_update_submitted>
  <last_update_submitted_qc>March 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 20, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Graz</investigator_affiliation>
    <investigator_full_name>Lerchbaum Elisabeth, MD</investigator_full_name>
    <investigator_title>A randomized, double-blind, placebo controlled trial to evaluate the effects of vitamin D</investigator_title>
  </responsible_party>
  <keyword>Polycystic Ovary Syndrome (PCOS)</keyword>
  <keyword>glucose metabolism</keyword>
  <keyword>Vitamin D deficiency</keyword>
  <keyword>vitamin D supplementation</keyword>
  <keyword>pharmakogenetics</keyword>
  <keyword>women</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</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>
  </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/NCT01721915
org study id: VitDPCOS1.0
secondary id: KLI 274
nct id: NCT01721915
lead sponsor: 
collaborator: 
has dmc: No
Background: Polycystic ovary syndrome (PCOS) is as common as 5-10% of all women in Austria.
      PCOS women frequently present with metabolic disturbances, hyperandrogenism and infertility.
      New therapy concepts are warranted. In our recent pilot study, vitamin D (vitD)
      supplementation significantly improved glucose metabolism and fertility. However, the
      efficacy of vitD administration shows individual variability indicating endogenous influences
      on pharmacological effects.

      A recent genome-wide association study reported three loci (DHCR7, CYP2R1, and GC) associated
      with vitD insufficiency. Moreover, vitD receptor (VDR) gene variants have already been known
      to be associated with insulin resistance.

      Aim: To test the hypothesis that vitD is efficient in changing metabolic parameters in PCOS
      and non-PCOS women longitudinally and to generate data on pharmacogenetic effects of vitD
      related genetic determinants adjusted for environmental factors.

      Primary outcome: Change from baseline in AUCgluc after vitD treatment. Secondary outcome: To
      generate the hypothesis that changes in metabolic and endocrine parameters following vitD
      treatment are associated with vitD related gene variants.

      Methods: 150 PCOS women with 25-hydroxyvitamin D (cholecalciferol, [25(OH)D]) levels <30
      ng/ml will be treated with vitD (20,000 IU/wk) or placebo in a 2:1 randomized controlled
      trial over 24 weeks and investigated for metabolic and endocrine parameters as well as vitD
      related genetic variants. In addition, 150 non-PCOS women with 25(OH)D <30 ng/ml will be
      treated with vitD (20,000 IU/wk) or placebo in a 2:1 randomized controlled trial over 24
      weeks and investigated for metabolic and endocrine parameters as well as vitD related genetic
      variants. The response to vitD supplementation in both groups will be analysed according to
      genotype profiles.

      Significance: VitD might be a new therapeutic option without major side effects for PCOS
      patients. Exploring specific loci for pharmacogenetic vitD actions would open a new window
      for therapy modulation in PCOS and other metabolic diseases.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCgluc
time frame: Change from Baseline in AUC gluc at 24 weeks
measure: Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR)
time frame: Change from Baseline in insulin resistance at 24 weeks
measure: Lipid levels (total cholesterol)
time frame: Change from Baseline in total cholesterol at 24 weeks
measure: HbA1c
time frame: Change from Baseline in HbA1c at 24 weeks
measure: Testosterone
time frame: Change from Baseline in testosterone at 24 weeks
measure: Menstrual frequency
time frame: Change from Baseline in menstrual frequency at 24 weeks
measure: Insulin sensitivity assessed by Quantitative Insulin-sensitivity Check Index (QUICKI)
time frame: Change from baseline in QUICKI at 24 weeks
measure: Free testosterone (FT)
time frame: Change from Baseline in FT at 4 weeks
measure: Triglycerides
time frame: Change from Baseline in triglycerides at 24 weeks
arm group label: Vitamin D supplementation
arm group type: Experimental
description: The treatment group will receive an oral dose of 20,000 IU vitD weekly (equivalent to 2857 IU/day) as oily drops (Oleovit D3-drops; producer: Fresenius Kabi Austria GmbH, Linz)
arm group label: Placebo
arm group type: Placebo Comparator
description: the placebo group will receive oily drops without vitD
intervention type: Drug
intervention name: Vitamin D supplementation
description: The treatment group will receive an oral dose of 20,000 IU vitD weekly (equivalent to 2857 IU/day) as oily drops (Oleovit D3-drops; producer: Fresenius Kabi Austria GmbH, Linz)
arm group label: Vitamin D supplementation
other name: A11CC05 Colecalciferol
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 44 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Elisabeth Lerchbaum, MD
role: Principal Investigator
affiliation: Medical University of Graz
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Graz
investigator full name: Lerchbaum Elisabeth, MD
investigator title: A randomized, double-blind, placebo controlled trial to evaluate the effects of vitamin D
mesh term: Polycystic Ovary Syndrome
mesh term: Vitamin D Deficiency
mesh term: Vitamin D