Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome: a Pilot Study (pilPregMet)
Primary Purpose
Polycystic Ovary Syndrome
Status
Completed
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Metformin
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Polycystic Ovary Syndrome focused on measuring Metformin, Pregnancy outcome, Androgens
Eligibility Criteria
Inclusion Criteria:
- diagnosis polycystic ovary syndrome (PCOS ) before pregnancy
- BMI 27-40 kg/m2
- Human chorionic gonadotropin, beta subunit (HCG-beta) verified pregnancy week 5-8
- At least one of the following criteria: (1) serum testosteron > 2,5 nmol/L; (2) Sex hormone binding globulin (SHBG) < 30 nmol; (3) Fasting C-peptid > 1,0 nmol/L; (4) Menstrual disturbances: oligo-/amenorrhea or metrorrhagia; (5) Hirsutism
Exclusion Criteria:
- known liver disease or ALAT > 60 IU/L
- S-creatinin > 130 micromol/L
- diabetes mellitus
- alcohol or drug abuse
- peroral steroid treatment (except inhalation steroids)
- use of cimetidine, anticoagulant, erythromycin or other macrolides
- not suitable for other reasons
Sites / Locations
- Departments of Obstetrics and Gynecology and Endocrinology, St. Olav's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metformin
placebo
Arm Description
Metformin 850 mg x 2 daily
Placebo 1 tablet x 2 daily
Outcomes
Primary Outcome Measures
Dehydroepiandrosterone sulfate (DHEAS)
(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)
Androstenedione
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
Testosterone
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
Sex hormone binding globulin (SHBG)
(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)
Free testosterone index
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)
Secondary Outcome Measures
Occurence of pregnancy complications
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
Pregnancy outcome - gestational age
Gestational age at birth (days)
Pregnancy outcome - gestational length
Gestational length (cm) measured at birth
Pregnancy outcome - head circumference
Head circumference (cm) measured at birth.
Pregnancy outcome - birthweight
Birthweight (g) measured at birth
Pregnancy outcome - placental weight
Placental weight (g) measured at birth
Pregnancy outcome - Agpar score at 5 minutes
Apgar score at 5 minutes
Pregnancy outcome - Agpar score at 10 minutes
Apgar score at 10 minutes
Pregnancy outcome - umbilical artery pH
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)
Full Information
NCT ID
NCT03259919
First Posted
August 17, 2017
Last Updated
October 16, 2018
Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03259919
Brief Title
Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome: a Pilot Study
Acronym
pilPregMet
Official Title
Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome: a Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
October 2000 (Actual)
Primary Completion Date
March 2003 (Actual)
Study Completion Date
March 2003 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome
Keywords
Metformin, Pregnancy outcome, Androgens
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metformin
Arm Type
Experimental
Arm Description
Metformin 850 mg x 2 daily
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo 1 tablet x 2 daily
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
metformin from Weifa 425 mg / tablet
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo from Weifa
Intervention 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.
Primary Outcome Measure Information:
Title
Dehydroepiandrosterone sulfate (DHEAS)
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)
Time Frame
up to delivery
Title
Androstenedione
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
Time Frame
up to delivery
Title
Testosterone
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
Time Frame
up to delivery
Title
Sex hormone binding globulin (SHBG)
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)
Time Frame
up to delivery
Title
Free testosterone index
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)
Time Frame
up to delivery
Secondary Outcome Measure Information:
Title
Occurence of pregnancy complications
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
Time Frame
up to 6 weeks post partum
Title
Pregnancy outcome - gestational age
Description
Gestational age at birth (days)
Time Frame
after delivery
Title
Pregnancy outcome - gestational length
Description
Gestational length (cm) measured at birth
Time Frame
after delivery
Title
Pregnancy outcome - head circumference
Description
Head circumference (cm) measured at birth.
Time Frame
after delivery
Title
Pregnancy outcome - birthweight
Description
Birthweight (g) measured at birth
Time Frame
after delivery
Title
Pregnancy outcome - placental weight
Description
Placental weight (g) measured at birth
Time Frame
after delivery
Title
Pregnancy outcome - Agpar score at 5 minutes
Description
Apgar score at 5 minutes
Time Frame
after delivery
Title
Pregnancy outcome - Agpar score at 10 minutes
Description
Apgar score at 10 minutes
Time Frame
after delivery
Title
Pregnancy outcome - umbilical artery pH
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)
Time Frame
after delivery
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
diagnosis polycystic ovary syndrome (PCOS ) before pregnancy
BMI 27-40 kg/m2
Human chorionic gonadotropin, beta subunit (HCG-beta) verified pregnancy week 5-8
At least one of the following criteria: (1) serum testosteron > 2,5 nmol/L; (2) Sex hormone binding globulin (SHBG) < 30 nmol; (3) Fasting C-peptid > 1,0 nmol/L; (4) Menstrual disturbances: oligo-/amenorrhea or metrorrhagia; (5) Hirsutism
Exclusion Criteria:
known liver disease or ALAT > 60 IU/L
S-creatinin > 130 micromol/L
diabetes mellitus
alcohol or drug abuse
peroral steroid treatment (except inhalation steroids)
use of cimetidine, anticoagulant, erythromycin or other macrolides
not suitable for other reasons
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sven M Carlsen, MD, PhD
Organizational Affiliation
Norwegian University of Science and Technology
Official's Role
Study Director
Facility Information:
Facility Name
Departments of Obstetrics and Gynecology and Endocrinology, St. Olav's Hospital
City
Trondheim
Country
Norway
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
15178665
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.
Results Reference
result
PubMed Identifier
29490031
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.
Results Reference
result
PubMed Identifier
35265033
Citation
Trouva A, Alvarsson M, Calissendorff J, Asvold BO, Vanky E, Hirschberg AL. Thyroid Status During Pregnancy in Women With Polycystic Ovary Syndrome and the Effect of Metformin. Front Endocrinol (Lausanne). 2022 Feb 21;13:772801. doi: 10.3389/fendo.2022.772801. eCollection 2022.
Results Reference
derived
PubMed Identifier
31613965
Citation
Underdal MO, Salvesen O, Henriksen AH, Andersen M, Vanky E. Impaired Respiratory Function in Women With PCOS Compared With Matched Controls From a Population-Based Study. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz053. doi: 10.1210/clinem/dgz053.
Results Reference
derived
PubMed Identifier
29659896
Citation
Underdal MO, Stridsklev S, Oppen IH, Hogetveit K, Andersen MS, Vanky E. Does Metformin Treatment During Pregnancy Modify the Future Metabolic Profile in Women With PCOS? J Clin Endocrinol Metab. 2018 Jun 1;103(6):2408-2413. doi: 10.1210/jc.2018-00485.
Results Reference
derived
Learn more about this trial
Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome: a Pilot Study
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