<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/NCT02187250</url>
  </required_header>
  <id_info>
    <org_study_id>DAXAS 2</org_study_id>
    <nct_id>NCT02187250</nct_id>
  </id_info>
  <brief_title>PDE-4 Inhibitor Roflumilast and GLP-1 Agonist Liraglutide in Polycystic Ovary Syndrome</brief_title>
  <official_title>Short-term Treatment With PDE-4 Inhibitor Roflumilast or GLP-1 Agonist Liraglutide or Metformin in Treatment Naive Obese Women With Polycystic Ovary Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Centre Ljubljana</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Centre Ljubljana</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study was to determine whether monotherapy treatment with&#xD;
      phosphodiesterase-4 (PDE-4) inhibitor roflumilast is more effective than treatment with&#xD;
      glucagon-like protein 1 (GLP-1) liraglutide or treatment with metformin as monotherapy in the&#xD;
      treatment of obese women with polycystic ovary syndrome (PCOS) regarding weight reduction who&#xD;
      have not been treated before. The investigators anticipated greater changes in body weight in&#xD;
      patients on roflumilast treatment than in liraglutide or metformin.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The main outcome was change in body weight.</measure>
    <time_frame>Patient's body weight was mesured at the base point and every four weeks during 12 weeks of clinical trial.</time_frame>
    <description>The patient's body weight was measured in kilograms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The secondary outcome was change in body mass index (BMI).</measure>
    <time_frame>Patient's body weight were measured at the basepoint and every four weeks during the 12 weeks of clinical trial. Patient's height was measured at the basepoint.</time_frame>
    <description>Patient's BMI was defined as the patient's body mass in kilograms divided by the square of their height in meters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The secondary outcome was change in waist circumference.</measure>
    <time_frame>Patient's waist circumference was measured at the basepoint and every four weeks during 12 weeks of clinical trial.</time_frame>
    <description>Patient's waist circumference was measured in centimeters.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The other outcomes was changes in fasting concentrations of glucose.</measure>
    <time_frame>Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.</time_frame>
    <description>Patient's blood was drawn between 8 and 9 a.m. Concentrations of fasting glucose was measured in mmol/L.</description>
  </other_outcome>
  <other_outcome>
    <measure>Other outcome was change in fasting concentration of insulin.</measure>
    <time_frame>Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.</time_frame>
    <description>Patient's blood was drawn between 8 and 9 a.m. Fasting concentrations of insulin was measured in mU/L.</description>
  </other_outcome>
  <other_outcome>
    <measure>Other outcome was change in blood concentrations of LH (luteinizing hormone).</measure>
    <time_frame>Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.</time_frame>
    <description>Patient's blood was drawn between 8 and 9 a.m. Concentration of LH was measured in U/L.</description>
  </other_outcome>
  <other_outcome>
    <measure>Other outcome was change in blood concentrations of FSH (follicle-stimulating hormone).</measure>
    <time_frame>Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.</time_frame>
    <description>Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of FSH was measured in U/L.</description>
  </other_outcome>
  <other_outcome>
    <measure>Other outcome was change in blood concentration of testosterone.</measure>
    <time_frame>Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.</time_frame>
    <description>Patient's blood was drawn between 8 and 9 a.m. Blood concentration was measured in nmol/L.</description>
  </other_outcome>
  <other_outcome>
    <measure>Other outcome was change in blood concentration in androstenedione.</measure>
    <time_frame>Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.</time_frame>
    <description>Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of androstenedione was measured in nmol/L.</description>
  </other_outcome>
  <other_outcome>
    <measure>Other outcome was change in blood concentrations of SHBG (sex hormone-binding globulin).</measure>
    <time_frame>Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.</time_frame>
    <description>Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of SHBG was measured in nmol/L.</description>
  </other_outcome>
  <other_outcome>
    <measure>Other outcome was change in blood concentration of DHEAS (dehydroepiandrosterone sulfate).</measure>
    <time_frame>Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.</time_frame>
    <description>Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of DHEAS was measured in micromol/L.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>PCOS</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>metformin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the metformin group metformin was initiated at a dose of 500 mg once per day and increased by 500 mg every 3 days up to 2x1000 mg BID per os.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>liraglutide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the liraglutide group liraglutide was initiated at a dose of 0,6mg sc once per day for one week and increased to 1,2mg sc one per day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>roflumilast</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the roflumilast group roflumilast was initiated at a dose of 500 mg BID per os.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metformin</intervention_name>
    <arm_group_label>metformin</arm_group_label>
    <other_name>Glucophage tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>liraglutide</intervention_name>
    <arm_group_label>liraglutide</arm_group_label>
    <other_name>Victoza injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>roflumilast</intervention_name>
    <arm_group_label>roflumilast</arm_group_label>
    <other_name>Daxas 500 micrograms film-coated tablets</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years old to menopause&#xD;
&#xD;
          -  polycystic ovary syndrome (NICHD criteria)&#xD;
&#xD;
          -  BMI of 30 kg/m² or higher&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  depression&#xD;
&#xD;
          -  type 1 or type 2 diabetes mellitus&#xD;
&#xD;
          -  history of carcinoma&#xD;
&#xD;
          -  history of pancreatitis&#xD;
&#xD;
          -  Cushing's syndrome or congenital (non-classic) adrenal hyperplasia&#xD;
&#xD;
          -  significant cardiovascular, kidney or hepatic disease&#xD;
&#xD;
          -  the use of medications other than metformin known or suspected to affect reproductive&#xD;
             or metabolic functions&#xD;
&#xD;
          -  the use of statins, within 90 days prior to study entry&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrej Janez, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Centre Ljubljana</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Center Ljubljana</name>
      <address>
        <city>Ljubljana</city>
        <zip>1000</zip>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Slovenia</country>
  </location_countries>
  <verification_date>June 2014</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>July 8, 2014</last_update_submitted>
  <last_update_submitted_qc>July 8, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 10, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Centre Ljubljana</investigator_affiliation>
    <investigator_full_name>Andrej Janez</investigator_full_name>
    <investigator_title>professor, MD, PhD</investigator_title>
  </responsible_party>
  <keyword>PCOS</keyword>
  <keyword>PDE-4 inhibitor</keyword>
  <keyword>roflumilast</keyword>
  <keyword>liraglutide</keyword>
  <keyword>metformin</keyword>
  <keyword>obesity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Liraglutide</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/NCT02187250
org study id: DAXAS 2
nct id: NCT02187250
lead sponsor: 
has dmc: No
The purpose of this study was to determine whether monotherapy treatment with
      phosphodiesterase-4 (PDE-4) inhibitor roflumilast is more effective than treatment with
      glucagon-like protein 1 (GLP-1) liraglutide or treatment with metformin as monotherapy in the
      treatment of obese women with polycystic ovary syndrome (PCOS) regarding weight reduction who
      have not been treated before. The investigators anticipated greater changes in body weight in
      patients on roflumilast treatment than in liraglutide or metformin.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The main outcome was change in body weight.
time frame: Patient's body weight was mesured at the base point and every four weeks during 12 weeks of clinical trial.
description: The patient's body weight was measured in kilograms.
measure: The secondary outcome was change in body mass index (BMI).
time frame: Patient's body weight were measured at the basepoint and every four weeks during the 12 weeks of clinical trial. Patient's height was measured at the basepoint.
description: Patient's BMI was defined as the patient's body mass in kilograms divided by the square of their height in meters.
measure: The secondary outcome was change in waist circumference.
time frame: Patient's waist circumference was measured at the basepoint and every four weeks during 12 weeks of clinical trial.
description: Patient's waist circumference was measured in centimeters.
measure: The other outcomes was changes in fasting concentrations of glucose.
time frame: Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.
description: Patient's blood was drawn between 8 and 9 a.m. Concentrations of fasting glucose was measured in mmol/L.
measure: Other outcome was change in fasting concentration of insulin.
time frame: Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.
description: Patient's blood was drawn between 8 and 9 a.m. Fasting concentrations of insulin was measured in mU/L.
measure: Other outcome was change in blood concentrations of LH (luteinizing hormone).
time frame: Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.
description: Patient's blood was drawn between 8 and 9 a.m. Concentration of LH was measured in U/L.
measure: Other outcome was change in blood concentrations of FSH (follicle-stimulating hormone).
time frame: Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.
description: Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of FSH was measured in U/L.
measure: Other outcome was change in blood concentration of testosterone.
time frame: Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.
description: Patient's blood was drawn between 8 and 9 a.m. Blood concentration was measured in nmol/L.
measure: Other outcome was change in blood concentration in androstenedione.
time frame: Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.
description: Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of androstenedione was measured in nmol/L.
measure: Other outcome was change in blood concentrations of SHBG (sex hormone-binding globulin).
time frame: Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.
description: Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of SHBG was measured in nmol/L.
measure: Other outcome was change in blood concentration of DHEAS (dehydroepiandrosterone sulfate).
time frame: Patient's fasting blood was drawn at the base point and at the endpoint of 12 weeks of clinical trial.
description: Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of DHEAS was measured in micromol/L.
arm group label: metformin
arm group type: Active Comparator
description: In the metformin group metformin was initiated at a dose of 500 mg once per day and increased by 500 mg every 3 days up to 2x1000 mg BID per os.
arm group label: liraglutide
arm group type: Active Comparator
description: In the liraglutide group liraglutide was initiated at a dose of 0,6mg sc once per day for one week and increased to 1,2mg sc one per day.
arm group label: roflumilast
arm group type: Active Comparator
description: In the roflumilast group roflumilast was initiated at a dose of 500 mg BID per os.
intervention type: Drug
intervention name: metformin
arm group label: metformin
other name: Glucophage tablets
intervention type: Drug
intervention name: liraglutide
arm group label: liraglutide
other name: Victoza injection
intervention type: Drug
intervention name: roflumilast
arm group label: roflumilast
other name: Daxas 500 micrograms film-coated tablets
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Andrej Janez, MD, PhD
role: Principal Investigator
affiliation: University Medical Centre Ljubljana
facility: 
country: Slovenia
responsible party type: Principal Investigator
investigator affiliation: University Medical Centre Ljubljana
investigator full name: Andrej Janez
investigator title: professor, MD, PhD
mesh term: Polycystic Ovary Syndrome
mesh term: Metformin
mesh term: Liraglutide