<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/NCT03259919</url>
  </required_header>
  <id_info>
    <org_study_id>220800</org_study_id>
    <nct_id>NCT03259919</nct_id>
  </id_info>
  <brief_title>Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome: a Pilot Study</brief_title>
  <acronym>pilPregMet</acronym>
  <official_title>Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome: a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Norwegian University of Science and Technology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>St. Olavs Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Norwegian University of Science and Technology</source>
  <oversight_info>
    <has_dmc>No</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>
      To investigate the effect of metformin on pregnancy complications and pregnancy outcome in&#xD;
      the II. and III. trimester of pregnancy in women with polycystic ovary syndrome.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2000</start_date>
  <completion_date type="Actual">March 2003</completion_date>
  <primary_completion_date type="Actual">March 2003</primary_completion_date>
  <phase>Phase 2</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dehydroepiandrosterone sulfate (DHEAS)</measure>
    <time_frame>up to delivery</time_frame>
    <description>(µmol/l) Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. Measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Androstenedione</measure>
    <time_frame>up to delivery</time_frame>
    <description>Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. measured by a double antibody technique on an Elecsys 2010 analyser (Roche Diagnostics GmbH, Germany) using reagents and calibrators supplied by the manufacturer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Testosterone</measure>
    <time_frame>up to delivery</time_frame>
    <description>Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. measured by a double antibody technique on an Elecsys 2010 analyser (Roche Diagnostics GmbH, Germany) using reagents and calibrators supplied by the manufacturer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sex hormone binding globulin (SHBG)</measure>
    <time_frame>up to delivery</time_frame>
    <description>(nmol/l) Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. Measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Free testosterone index</measure>
    <time_frame>up to delivery</time_frame>
    <description>Calculated as total testosterone divided by SHBG and multiplied by a factor of 100. SHBG measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurence of pregnancy complications</measure>
    <time_frame>up to 6 weeks post partum</time_frame>
    <description>Gestational diabetes (GDM) defined according to World Health Organization (1998) criteria, i.e. 2 h plasma glucose values ≥7.8 mmol/l during an Oral Glucose Tolerance Test (OGTT) with 75 g. Uncomplicated GDM treated with dietary advice only was not ranked among the complications in this study. Pre-eclampsia defined as a blood pressure ≥140/90mmHg with concomitant albuminuria ≥0.3 g/24 h measured on two separate occasions after gestational week 20. Premature delivery was defined as delivery before gestational week 37 + 0 according to an estimated date of delivery, based on mid-trimester ultrasound scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome - gestational age</measure>
    <time_frame>after delivery</time_frame>
    <description>Gestational age at birth (days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome - gestational length</measure>
    <time_frame>after delivery</time_frame>
    <description>Gestational length (cm) measured at birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome - head circumference</measure>
    <time_frame>after delivery</time_frame>
    <description>Head circumference (cm) measured at birth.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome - birthweight</measure>
    <time_frame>after delivery</time_frame>
    <description>Birthweight (g) measured at birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome - placental weight</measure>
    <time_frame>after delivery</time_frame>
    <description>Placental weight (g) measured at birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome - Agpar score at 5 minutes</measure>
    <time_frame>after delivery</time_frame>
    <description>Apgar score at 5 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome - Agpar score at 10 minutes</measure>
    <time_frame>after delivery</time_frame>
    <description>Apgar score at 10 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome - umbilical artery pH</measure>
    <time_frame>after delivery</time_frame>
    <description>Umbilical artery pH measured in umbilical artery blood, immediately after delivery on a Rapidlab 248pH/Blood Gas Analyzer, using reagents and calibrators supplied by the manufacturer (Bayer Corp., USA)</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>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metformin 850 mg x 2 daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 1 tablet x 2 daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin 850 mg x 1 per day for the first week, and 850 mg x 2 per day for the rest of the study period.. Orally. From inclusion (before gestational week 8) to delivery. Verbal and written diet and lifestyle advices at inclusion to the study. In addition 1 mg tablet of folate and one daily multivitamin tablet.</description>
    <arm_group_label>Metformin</arm_group_label>
    <other_name>metformin from Weifa 425 mg / tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo, 2 tablets x 1 daily for the first week, and 2 tablets x 2 for the rest of the study period.Orally. From inclusion (that is before gestational week 12) to delivery. Verbal and written diet and lifestyle advices at inclusion to the study. In addition 1 mg tablet of folate and one daily multivitamin tablet.</description>
    <arm_group_label>placebo</arm_group_label>
    <other_name>Placebo from Weifa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  diagnosis polycystic ovary syndrome (PCOS ) before pregnancy&#xD;
&#xD;
          -  BMI 27-40 kg/m2&#xD;
&#xD;
          -  Human chorionic gonadotropin, beta subunit (HCG-beta) verified pregnancy week 5-8&#xD;
&#xD;
          -  At least one of the following criteria: (1) serum testosteron &gt; 2,5 nmol/L; (2) Sex&#xD;
             hormone binding globulin (SHBG) &lt; 30 nmol; (3) Fasting C-peptid &gt; 1,0 nmol/L; (4)&#xD;
             Menstrual disturbances: oligo-/amenorrhea or metrorrhagia; (5) Hirsutism&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known liver disease or ALAT &gt; 60 IU/L&#xD;
&#xD;
          -  S-creatinin &gt; 130 micromol/L&#xD;
&#xD;
          -  diabetes mellitus&#xD;
&#xD;
          -  alcohol or drug abuse&#xD;
&#xD;
          -  peroral steroid treatment (except inhalation steroids)&#xD;
&#xD;
          -  use of cimetidine, anticoagulant, erythromycin or other macrolides&#xD;
&#xD;
          -  not suitable for other reasons&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sven M Carlsen, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Norwegian University of Science and Technology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Departments of Obstetrics and Gynecology and Endocrinology, St. Olav's Hospital</name>
      <address>
        <city>Trondheim</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <results_reference>
    <citation>Vanky E, Salvesen KA, Heimstad R, Fougner KJ, Romundstad P, Carlsen SM. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Hum Reprod. 2004 Aug;19(8):1734-40. doi: 10.1093/humrep/deh347. Epub 2004 Jun 3.</citation>
    <PMID>15178665</PMID>
  </results_reference>
  <results_reference>
    <citation>Hanem LGE, Stridsklev S, Juliusson PB, Salvesen O, Roelants M, Carlsen SM, Odegard R, Vanky E. Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1612-1621. doi: 10.1210/jc.2017-02419.</citation>
    <PMID>29490031</PMID>
  </results_reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>October 16, 2018</last_update_submitted>
  <last_update_submitted_qc>October 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metformin</keyword>
  <keyword>Pregnancy outcome</keyword>
  <keyword>Androgens</keyword>
  <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>
  </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/NCT03259919
org study id: 220800
nct id: NCT03259919
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To investigate the effect of metformin on pregnancy complications and pregnancy outcome in
      the II. and III. trimester of pregnancy in women with polycystic ovary syndrome.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Dehydroepiandrosterone sulfate (DHEAS)
time frame: up to delivery
description: (µmol/l) Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. Measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA)
measure: Androstenedione
time frame: up to delivery
description: Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. measured by a double antibody technique on an Elecsys 2010 analyser (Roche Diagnostics GmbH, Germany) using reagents and calibrators supplied by the manufacturer
measure: Testosterone
time frame: up to delivery
description: Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. measured by a double antibody technique on an Elecsys 2010 analyser (Roche Diagnostics GmbH, Germany) using reagents and calibrators supplied by the manufacturer
measure: Sex hormone binding globulin (SHBG)
time frame: up to delivery
description: (nmol/l) Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. Measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA)
measure: Free testosterone index
time frame: up to delivery
description: Calculated as total testosterone divided by SHBG and multiplied by a factor of 100. SHBG measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA)
measure: Occurence of pregnancy complications
time frame: up to 6 weeks post partum
description: Gestational diabetes (GDM) defined according to World Health Organization (1998) criteria, i.e. 2 h plasma glucose values ≥7.8 mmol/l during an Oral Glucose Tolerance Test (OGTT) with 75 g. Uncomplicated GDM treated with dietary advice only was not ranked among the complications in this study. Pre-eclampsia defined as a blood pressure ≥140/90mmHg with concomitant albuminuria ≥0.3 g/24 h measured on two separate occasions after gestational week 20. Premature delivery was defined as delivery before gestational week 37 + 0 according to an estimated date of delivery, based on mid-trimester ultrasound scan
measure: Pregnancy outcome - gestational age
time frame: after delivery
description: Gestational age at birth (days)
measure: Pregnancy outcome - gestational length
time frame: after delivery
description: Gestational length (cm) measured at birth
measure: Pregnancy outcome - head circumference
time frame: after delivery
description: Head circumference (cm) measured at birth.
measure: Pregnancy outcome - birthweight
time frame: after delivery
description: Birthweight (g) measured at birth
measure: Pregnancy outcome - placental weight
time frame: after delivery
description: Placental weight (g) measured at birth
measure: Pregnancy outcome - Agpar score at 5 minutes
time frame: after delivery
description: Apgar score at 5 minutes
measure: Pregnancy outcome - Agpar score at 10 minutes
time frame: after delivery
description: Apgar score at 10 minutes
measure: Pregnancy outcome - umbilical artery pH
time frame: after delivery
description: Umbilical artery pH measured in umbilical artery blood, immediately after delivery on a Rapidlab 248pH/Blood Gas Analyzer, using reagents and calibrators supplied by the manufacturer (Bayer Corp., USA)
arm group label: Metformin
arm group type: Experimental
description: Metformin 850 mg x 2 daily
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo 1 tablet x 2 daily
intervention type: Drug
intervention name: Metformin
description: Metformin 850 mg x 1 per day for the first week, and 850 mg x 2 per day for the rest of the study period.. Orally. From inclusion (before gestational week 8) to delivery. Verbal and written diet and lifestyle advices at inclusion to the study. In addition 1 mg tablet of folate and one daily multivitamin tablet.
arm group label: Metformin
other name: metformin from Weifa 425 mg / tablet
intervention type: Drug
intervention name: Placebo
description: Placebo, 2 tablets x 1 daily for the first week, and 2 tablets x 2 for the rest of the study period.Orally. From inclusion (that is before gestational week 12) to delivery. Verbal and written diet and lifestyle advices at inclusion to the study. In addition 1 mg tablet of folate and one daily multivitamin tablet.
arm group label: placebo
other name: Placebo from Weifa
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Sven M Carlsen, MD, PhD
role: Study Director
affiliation: Norwegian University of Science and Technology
facility: 
country: Norway
citation: Vanky E, Salvesen KA, Heimstad R, Fougner KJ, Romundstad P, Carlsen SM. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Hum Reprod. 2004 Aug;19(8):1734-40. doi: 10.1093/humrep/deh347. Epub 2004 Jun 3.
PMID: 15178665
citation: Hanem LGE, Stridsklev S, Juliusson PB, Salvesen O, Roelants M, Carlsen SM, Odegard R, Vanky E. Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1612-1621. doi: 10.1210/jc.2017-02419.
PMID: 29490031
responsible party type: Sponsor
mesh term: Polycystic Ovary Syndrome
mesh term: Syndrome
mesh term: Metformin
sharing ipd: No