<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/NCT03008551</url>
  </required_header>
  <id_info>
    <org_study_id>Version 3.0</org_study_id>
    <nct_id>NCT03008551</nct_id>
  </id_info>
  <brief_title>Empagliflozin vs Metformin in PCOS</brief_title>
  <official_title>The Effect of Empagliflozin Versus Metformin on Hormonal, Metabolic and Cardiovascular Risk Factors in Patients With Polycystic Ovary Syndrome (PCOS) - a Randomised Open-label Parallel Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hull University Teaching Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hull University Teaching Hospitals NHS Trust</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This a randomised open-label parallel study involving women with polycystic ovary syndrome&#xD;
      (PCOS). The patients will be randomised either to metformin 1500mg or empagliflozin 25mg&#xD;
      daily for three months. The aim of the study is to examine the effect of empagliflozin on&#xD;
      hormonal, metabolic and cardiovascular risk markers and quality of life in women with PCOS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Polycystic ovary syndrome (PCOS) is a very common condition in women that may present with&#xD;
      irregular periods, excessive hair growth on the face and body, acne and cysts in the ovaries.&#xD;
      PCOS is also associated with increased risk of problems later in life like diabetes, high&#xD;
      cholesterol levels and heart disease.&#xD;
&#xD;
      In this study, a medication named Empagliflozin will be tested. Empagliflozin belongs to a&#xD;
      class of medicines known as SGLT-2 inhibitors. SGLT-2 stands for sodium glucose&#xD;
      co-transporter 2. Empagliflozin, in simple terms, helps in reducing high blood glucose levels&#xD;
      by increasing the amount of glucose passed in your urine. This medicine is usually used in&#xD;
      patients with type 2 diabetes and has led to improved blood pressure and weight loss in&#xD;
      addition to improving blood glucose levels.&#xD;
&#xD;
      We want to give Empagliflozin to women with PCOS to see its effect on hormones related to&#xD;
      PCOS and the risk factors for diabetes and heart disease. We will be comparing its effects to&#xD;
      metformin (another drug for diabetes) which has already been used in PCOS with very good&#xD;
      results.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 18, 2017</start_date>
  <completion_date type="Actual">April 2, 2018</completion_date>
  <primary_completion_date type="Actual">April 2, 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endothelial function as measured by RHI (reactive hyperaemia index).</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin 1500mg daily</time_frame>
    <description>Endothelial function as measured by RHI (reactive hyperaemia index) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Inflammatory markers (hsCRP)</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin 1500mg daily</time_frame>
    <description>Inflammatory markers (hsCRP) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin resistance as measured by HOMA (fasting glucose &amp; insulin)</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin 1500mg daily</time_frame>
    <description>Insulin resistance as measured by HOMA (fasting glucose &amp; insulin) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body weight</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin 1500mg daily</time_frame>
    <description>Body weight will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin 1500mg daily</time_frame>
    <description>Blood pressure will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin 1500mg daily</time_frame>
    <description>Lipid profile will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hormonal parameters including free androgen index</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin 1500mg daily</time_frame>
    <description>Hormonal parameters including free androgen index will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial function measured by microparticles</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin 1500mg daily</time_frame>
    <description>Endothelial function measured by microparticles will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life Questionnaire</measure>
    <time_frame>Three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</time_frame>
    <description>Quality of life will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Polycystic Ovary Syndrome</condition>
  <arm_group>
    <arm_group_label>Empagliflozin group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive empagliflozin 25mg daily for 3 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Each participant will receive metformin 1500mg daily for 3 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Empagliflozin</intervention_name>
    <description>Each participant will receive empagliflozin 25mg daily for 3 months.</description>
    <arm_group_label>Empagliflozin group</arm_group_label>
    <other_name>Jardiance</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Each participant will receive metformin 1500mg daily for 3 months.</description>
    <arm_group_label>Metformin group</arm_group_label>
    <other_name>Glucophage SR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women, aged 18-45 years (inclusive), with confirmed diagnosis of PCOS based on&#xD;
             Rotterdam criteria.&#xD;
&#xD;
          2. Presence of both irregular periods and biochemical hyperandrogenaemia&#xD;
&#xD;
          3. Body mass index ≥25&#xD;
&#xD;
          4. Negative pregnancy test during screening visit and agree to use barrier contraception&#xD;
             during the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non-classical 21-hydroxylase deficiency, hyperprolactinaemia, Cushing's disease and&#xD;
             androgen-secreting tumours will be excluded by appropriate tests.&#xD;
&#xD;
          2. Confirmed diagnosis of diabetes or pre-diabetes.&#xD;
&#xD;
          3. Ongoing, inadequately controlled thyroid disorder (subjects on thyroid hormone&#xD;
             replacement therapy must be on stable dose for at least 3 months before screening day)&#xD;
&#xD;
          4. History or presence of malignant neoplasms within the last 5 years (except basal and&#xD;
             squamous cell skin cancer and in-situ carcinoma).&#xD;
&#xD;
          5. History or plan of any form of gastrointestinal tract surgery.&#xD;
&#xD;
          6. History of pancreatitis (Acute or Chronic).&#xD;
&#xD;
          7. Any disorder which in the opinion of the investigator might jeopardize subject's&#xD;
             safety.&#xD;
&#xD;
          8. Subjects who are on any of the following medications within 3 months of recruitment:&#xD;
&#xD;
               -  Metformin or other insulin-sensitizing medications (e.g., pioglitazone )&#xD;
&#xD;
               -  Hormonal contraceptives (e.g., birth control pills, hormone-releasing implants,&#xD;
                  etc.)&#xD;
&#xD;
               -  Anti-androgens (e.g., spironolactone, flutamide, finasteride, etc.)&#xD;
&#xD;
               -  Clomiphene citrate or estrogen modulators such as letrozole&#xD;
&#xD;
               -  GnRH modulators such as leuprolide&#xD;
&#xD;
               -  Minoxidil&#xD;
&#xD;
          9. Female who is pregnant, breast feeding or intended to become pregnant or of child&#xD;
             bearing potential not using adequate contraceptive methods.&#xD;
&#xD;
         10. eGFR&lt;60&#xD;
&#xD;
         11. Hypersensitivity to lactose&#xD;
&#xD;
         12. Severe hepatic impairment (ALT &gt;3 times ULN)&#xD;
&#xD;
         13. Women with history of recurrent urinary tract infections.&#xD;
&#xD;
         14. Haematocrit above the upper limit of normal range.&#xD;
&#xD;
         15. Have been involved in another medicinal trial (CTIMP) within the past four weeks.&#xD;
&#xD;
         16. Known hypersensitivity to the Investigational Medicinal Products or any of their&#xD;
             excipients.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thozhukat Sathyapalan, MBBS FRCP MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Hull/Hull and East Yorkshire Hospitals NHS Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Michael White Centre for Diabetes and Endocrinology</name>
      <address>
        <city>Hull</city>
        <state>East Yorkshire</state>
        <zip>HU3 2RW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Javed Z, Papageorgiou M, Deshmukh H, Rigby AS, Qamar U, Abbas J, Khan AY, Kilpatrick ES, Atkin SL, Sathyapalan T. Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study. Clin Endocrinol (Oxf). 2019 Jun;90(6):805-813. doi: 10.1111/cen.13968. Epub 2019 Apr 2.</citation>
    <PMID>30866088</PMID>
  </results_reference>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>July 11, 2019</last_update_submitted>
  <last_update_submitted_qc>July 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2019</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>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>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>Empagliflozin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03008551
org study id: Version 3.0
nct id: NCT03008551
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This a randomised open-label parallel study involving women with polycystic ovary syndrome
      (PCOS). The patients will be randomised either to metformin 1500mg or empagliflozin 25mg
      daily for three months. The aim of the study is to examine the effect of empagliflozin on
      hormonal, metabolic and cardiovascular risk markers and quality of life in women with PCOS.
Polycystic ovary syndrome (PCOS) is a very common condition in women that may present with
      irregular periods, excessive hair growth on the face and body, acne and cysts in the ovaries.
      PCOS is also associated with increased risk of problems later in life like diabetes, high
      cholesterol levels and heart disease.

      In this study, a medication named Empagliflozin will be tested. Empagliflozin belongs to a
      class of medicines known as SGLT-2 inhibitors. SGLT-2 stands for sodium glucose
      co-transporter 2. Empagliflozin, in simple terms, helps in reducing high blood glucose levels
      by increasing the amount of glucose passed in your urine. This medicine is usually used in
      patients with type 2 diabetes and has led to improved blood pressure and weight loss in
      addition to improving blood glucose levels.

      We want to give Empagliflozin to women with PCOS to see its effect on hormones related to
      PCOS and the risk factors for diabetes and heart disease. We will be comparing its effects to
      metformin (another drug for diabetes) which has already been used in PCOS with very good
      results.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Endothelial function as measured by RHI (reactive hyperaemia index).
time frame: Three months treatment with either empagliflozin 25mg or metformin 1500mg daily
description: Endothelial function as measured by RHI (reactive hyperaemia index) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
measure: Inflammatory markers (hsCRP)
time frame: Three months treatment with either empagliflozin 25mg or metformin 1500mg daily
description: Inflammatory markers (hsCRP) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
measure: Insulin resistance as measured by HOMA (fasting glucose & insulin)
time frame: Three months treatment with either empagliflozin 25mg or metformin 1500mg daily
description: Insulin resistance as measured by HOMA (fasting glucose & insulin) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
measure: Body weight
time frame: Three months treatment with either empagliflozin 25mg or metformin 1500mg daily
description: Body weight will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
measure: Blood pressure
time frame: Three months treatment with either empagliflozin 25mg or metformin 1500mg daily
description: Blood pressure will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
measure: Lipid profile
time frame: Three months treatment with either empagliflozin 25mg or metformin 1500mg daily
description: Lipid profile will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
measure: Hormonal parameters including free androgen index
time frame: Three months treatment with either empagliflozin 25mg or metformin 1500mg daily
description: Hormonal parameters including free androgen index will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
measure: Endothelial function measured by microparticles
time frame: Three months treatment with either empagliflozin 25mg or metformin 1500mg daily
description: Endothelial function measured by microparticles will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
measure: Quality of life Questionnaire
time frame: Three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
description: Quality of life will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily
arm group label: Empagliflozin group
arm group type: Experimental
description: Each participant will receive empagliflozin 25mg daily for 3 months
arm group label: Metformin group
arm group type: Active Comparator
description: Each participant will receive metformin 1500mg daily for 3 months
intervention type: Drug
intervention name: Empagliflozin
description: Each participant will receive empagliflozin 25mg daily for 3 months.
arm group label: Empagliflozin group
other name: Jardiance
intervention type: Drug
intervention name: Metformin
description: Each participant will receive metformin 1500mg daily for 3 months.
arm group label: Metformin group
other name: Glucophage SR
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Thozhukat Sathyapalan, MBBS FRCP MD
role: Principal Investigator
affiliation: University of Hull/Hull and East Yorkshire Hospitals NHS Trust
facility: 
country: United Kingdom
citation: Javed Z, Papageorgiou M, Deshmukh H, Rigby AS, Qamar U, Abbas J, Khan AY, Kilpatrick ES, Atkin SL, Sathyapalan T. Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study. Clin Endocrinol (Oxf). 2019 Jun;90(6):805-813. doi: 10.1111/cen.13968. Epub 2019 Apr 2.
PMID: 30866088
responsible party type: Sponsor
mesh term: Polycystic Ovary Syndrome
mesh term: Syndrome
mesh term: Metformin
mesh term: Empagliflozin
sharing ipd: No