<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/NCT03034941</url>
  </required_header>
  <id_info>
    <org_study_id>Obesity,PCOS and IVF</org_study_id>
    <nct_id>NCT03034941</nct_id>
  </id_info>
  <brief_title>Short Term Weight Loss With Liraglutide and Metformin in Infertile Obese PCOS Patients</brief_title>
  <official_title>Short Term Weight Loss With Liraglutide and Metformin Before IVF in Infertile Obese PCOS Patients</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 aim of this study was to evaluate the impact of short-term weight reduction achieved with&#xD;
      12-week intervention with metformin alone or in combination with liraglutide on oocyte&#xD;
      maturity and embryo quality in infertile obese PCOS population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, in&#xD;
      particular when PCOS is linked to obesity. Obese PCOS has poor IVF outcomes associated with&#xD;
      impaired oocyte and embryo parameters and morphology. The purpose of this pilot prospective&#xD;
      study was to investigate the effect of the antiobesity medical therapy (combination of&#xD;
      metformin and liraglutide (COMBI)) on short time weight loss in the specific infertile obese&#xD;
      PCOS population. Additionally, we analyzed eventual impact of the short term weight loss 5%&#xD;
      or more before IVF on oocyte maturity and embryo quality in infertile obese PCOS population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</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 BMI</measure>
    <time_frame>Patient's BMI was measured at the beginning and every four weeks during 12 weeks of clinical trial.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Impact of the short term weight loss 5% or more before IVF on oocyte maturity in infertile obese PCOS population.</measure>
    <time_frame>patients were introduced to IVF one month after completed weight loss therapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of the short term weight loss 5% or more before IVF on oocyte number of blastocysts in infertile obese PCOS population.</measure>
    <time_frame>patients were introduced to IVF one month after completed weight loss therapy</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Obesity</condition>
  <condition>PCOS</condition>
  <arm_group>
    <arm_group_label>metformin group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: metformin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>COMBI group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: liraglutide + metformin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CONTROL group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>control group of obese PCOS patients without therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <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 1000 mg twice per day per os for 12 weeks</description>
    <arm_group_label>COMBI group</arm_group_label>
    <arm_group_label>metformin group</arm_group_label>
    <other_name>Glucophage tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liraglutide + metformin</intervention_name>
    <description>In the COMBI group the initial dose of metformin was 500 mg for at least 2 wk and gradually increased to a final dose of 1000 mg twice per day. Liraglutide 1.2 mg once per day s.c. was added after first two weeks of monotherapy with metformin.</description>
    <arm_group_label>COMBI group</arm_group_label>
    <other_name>Victoza 6 mg/ml solution and Glucophage tablets</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  polycystic ovary syndrome (rotterdam criteria)&#xD;
&#xD;
          -  BMI of 30 kg/m² or higher&#xD;
&#xD;
          -  Infertility for IVF with normal male sperm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  type 1 or type 2 diabetes mellitus&#xD;
&#xD;
          -  history of carcinoma&#xD;
&#xD;
          -  Cushing's syndrome or congenital (non-classic) adrenal hyperplasia&#xD;
&#xD;
          -  personal or family history of multiple endocrine neoplasia 2&#xD;
&#xD;
          -  significant cardiovascular, kidney or hepatic disease&#xD;
&#xD;
          -  the use of medications known or suspected to affect reproductive or metabolic&#xD;
             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>38 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eda Vrtacnik Bokal, professor</last_name>
    <role>Study Chair</role>
    <affiliation>University Medical Centre Ljubljana</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Center Ljubljana</name>
      <address>
        <city>Ljubljana</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Slovenia</country>
  </location_countries>
  <reference>
    <citation>Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. Print 2014 Mar.</citation>
    <PMID>24362411</PMID>
  </reference>
  <reference>
    <citation>Jungheim ES, Lanzendorf SE, Odem RR, Moley KH, Chang AS, Ratts VS. Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome. Fertil Steril. 2009 Jul;92(1):256-61. doi: 10.1016/j.fertnstert.2008.04.063. Epub 2008 Aug 9.</citation>
    <PMID>18692801</PMID>
  </reference>
  <reference>
    <citation>Depalo R, Garruti G, Totaro I, Panzarino M, Vacca MP, Giorgino F, Selvaggi LE. Oocyte morphological abnormalities in overweight women undergoing in vitro fertilization cycles. Gynecol Endocrinol. 2011 Nov;27(11):880-4. doi: 10.3109/09513590.2011.569600. Epub 2011 Apr 18.</citation>
    <PMID>21500991</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <last_update_submitted>January 25, 2017</last_update_submitted>
  <last_update_submitted_qc>January 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 27, 2017</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>Obesity</keyword>
  <keyword>PCOS</keyword>
  <keyword>Infertility</keyword>
  <keyword>Liraglutide</keyword>
  <keyword>Metformin</keyword>
  <keyword>IVF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Weight Loss</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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data are going to be available for other researchers if needed after the evaluation of this study.</ipd_description>
  </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/NCT03034941
org study id: Obesity,PCOS and IVF
nct id: NCT03034941
lead sponsor: 
has dmc: No
The aim of this study was to evaluate the impact of short-term weight reduction achieved with
      12-week intervention with metformin alone or in combination with liraglutide on oocyte
      maturity and embryo quality in infertile obese PCOS population.
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, in
      particular when PCOS is linked to obesity. Obese PCOS has poor IVF outcomes associated with
      impaired oocyte and embryo parameters and morphology. The purpose of this pilot prospective
      study was to investigate the effect of the antiobesity medical therapy (combination of
      metformin and liraglutide (COMBI)) on short time weight loss in the specific infertile obese
      PCOS population. Additionally, we analyzed eventual impact of the short term weight loss 5%
      or more before IVF on oocyte maturity and embryo quality in infertile obese PCOS population.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The main outcome was change in BMI
time frame: Patient's BMI was measured at the beginning and every four weeks during 12 weeks of clinical trial.
measure: Impact of the short term weight loss 5% or more before IVF on oocyte maturity in infertile obese PCOS population.
time frame: patients were introduced to IVF one month after completed weight loss therapy
measure: Impact of the short term weight loss 5% or more before IVF on oocyte number of blastocysts in infertile obese PCOS population.
time frame: patients were introduced to IVF one month after completed weight loss therapy
arm group label: metformin group
arm group type: Active Comparator
description: Drug: metformin
arm group label: COMBI group
arm group type: Active Comparator
description: Drug: liraglutide + metformin
arm group label: CONTROL group
arm group type: No Intervention
description: control group of obese PCOS patients without therapy
intervention type: Drug
intervention name: Metformin
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 1000 mg twice per day per os for 12 weeks
arm group label: COMBI group
arm group label: metformin group
other name: Glucophage tablets
intervention type: Drug
intervention name: Liraglutide + metformin
description: In the COMBI group the initial dose of metformin was 500 mg for at least 2 wk and gradually increased to a final dose of 1000 mg twice per day. Liraglutide 1.2 mg once per day s.c. was added after first two weeks of monotherapy with metformin.
arm group label: COMBI group
other name: Victoza 6 mg/ml solution and Glucophage tablets
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 38 Years
healthy volunteers: No
last name: Eda Vrtacnik Bokal, professor
role: Study Chair
affiliation: University Medical Centre Ljubljana
facility: 
country: Slovenia
citation: Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. Print 2014 Mar.
PMID: 24362411
citation: Jungheim ES, Lanzendorf SE, Odem RR, Moley KH, Chang AS, Ratts VS. Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome. Fertil Steril. 2009 Jul;92(1):256-61. doi: 10.1016/j.fertnstert.2008.04.063. Epub 2008 Aug 9.
PMID: 18692801
citation: Depalo R, Garruti G, Totaro I, Panzarino M, Vacca MP, Giorgino F, Selvaggi LE. Oocyte morphological abnormalities in overweight women undergoing in vitro fertilization cycles. Gynecol Endocrinol. 2011 Nov;27(11):880-4. doi: 10.3109/09513590.2011.569600. Epub 2011 Apr 18.
PMID: 21500991
responsible party type: Principal Investigator
investigator affiliation: University Medical Centre Ljubljana
investigator full name: Andrej Janez
investigator title: professor, MD, PhD
mesh term: Weight Loss
mesh term: Metformin
mesh term: Liraglutide
sharing ipd: Yes
ipd description: Data are going to be available for other researchers if needed after the evaluation of this study.