Clinical trial NCT00159536: Metformin in Pregnant PCOS Women
Official title: Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome (PCOS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polycystic Ovary Syndrome
Keywords: PCOS
metformin
pregnancy
preeclampsia
diabetes
preterm delivery
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: St. Olavs Hospital
First posted: 2005-09-12
Enrollment: 257
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 18-45 years,
* PCOS diagnosis according to Rotterdam criteria
* single, viable, ultrasound verified fetus
* if metformin was used at conception and early pregnancy, at least 7 days of "wash out"

Exclusion Criteria:

* known liver disease or ALAT \> 90 nmol/L
* known renal disease or creatinine \> 110 micromol/L
* diabetes mellitus
* alcohol or drug abuse
* peroral steroid treatment
* cimetidine, anticoagulant or erythromycin treatment at time of inclusion
* not suitable for other reasons

Primary outcomes:
measure: Gestational diabetes
timeFrame: up to delivery
measure: incidence of metabolic syndrome and neurophysiologic parameters in offspring
timeFrame: Within 18 years
measure: Preterm delivery
timeFrame: up to delivery
measure: pre-eclampsia
timeFrame: up to delivery
Secondary outcomes:
measure: emesis and hyperemesis
timeFrame: up to delivery
measure: Breastfeeding
timeFrame: One year post partum
measure: weight change
timeFrame: up to delivery
measure: blood pressure change
timeFrame: up to delivery
measure: Incident of instrumental deliveries
timeFrame: at delivery
measure: Hormone levels in mother and offspring
timeFrame: up to delivery
measure: Snoring and sleep quality
timeFrame: up to delivery
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: University hospital of Bergen
city: Bodø
country: Norway
facility: Central Hospital of Northern Norway
city: Drammen
country: Norway
facility: Buskerud Hospital
city: Haugesund
country: Norway
facility: Haugesund Hospital
city: Hønefoss
country: Norway
facility: Ringerike Hospital
city: Kristiansand
country: Norway
facility: Elvebredden Gynekologpraksis
city: Lillehammer
country: Norway
facility: Lillehammer Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Trondheim
country: Norway
facility: Departments of Obstetrics and Gynecology and Endocrinology, St. Olav's Hospital
city: Ålesund
country: Norway
facility: Ålesund Hospital
Study officials:
affiliation: Norwegian University of Science and Technology
name: Eszter I Vanky, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Vanky E, Stridsklev S, Heimstad R, Romundstad P, Skogoy K, Kleggetveit O, Hjelle S, von Brandis P, Eikeland T, Flo K, Berg KF, Bunford G, Lund A, Bjerke C, Almas I, Berg AH, Danielson A, Lahmami G, Carlsen SM. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab. 2010 Dec;95(12):E448-55. doi: 10.1210/jc.2010-0853. Epub 2010 Oct 6.
citation: Vanky E, Carlsen SM. Androgens and antimullerian hormone in mothers with polycystic ovary syndrome and their newborns. Fertil Steril. 2012 Feb;97(2):509-15. doi: 10.1016/j.fertnstert.2011.11.021. Epub 2011 Dec 10.
citation: Shetelig Lovvik T, Stridsklev S, Carlsen SM, Salvesen O, Vanky E. Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect? J Clin Endocrinol Metab. 2016 Jun;101(6):2325-31. doi: 10.1210/jc.2015-3498. Epub 2016 Feb 2.
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: Hanem LGE, Salvesen O, Juliusson PB, Carlsen SM, Nossum MCF, Vaage MO, Odegard R, Vanky E. Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5-10 year follow-up of the PregMet randomised controlled trial. Lancet Child Adolesc Health. 2019 Mar;3(3):166-174. doi: 10.1016/S2352-4642(18)30385-7. Epub 2019 Jan 29.
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.
citation: Stokkeland LMT, Giskeodegard GF, Ryssdal M, Jarmund AH, Steinkjer B, Madssen TS, Stafne SN, Stridsklev S, Lovvik TS, Iversen AC, Vanky E. Changes in Serum Cytokines Throughout Pregnancy in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2022 Jan 1;107(1):39-52. doi: 10.1210/clinem/dgab684.
citation: Andrae F, Abbott D, Stridsklev S, Schmedes AV, Odsaeter IH, Vanky E, Salvesen O. Sustained Maternal Hyperandrogenism During PCOS Pregnancy Reduced by Metformin in Non-obese Women Carrying a Male Fetus. J Clin Endocrinol Metab. 2020 Dec 1;105(12):3762-70. doi: 10.1210/clinem/dgaa605.
citation: Greger HK, Hanem LGE, Ostgard HF, Vanky E. Cognitive function in metformin exposed children, born to mothers with PCOS - follow-up of an RCT. BMC Pediatr. 2020 Feb 10;20(1):60. doi: 10.1186/s12887-020-1960-2.
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.
citation: Stridsklev S, Salvesen O, Salvesen KA, Carlsen SM, Vanky E. Uterine Artery Doppler in Pregnancy: Women with PCOS Compared to Healthy Controls. Int J Endocrinol. 2018 Aug 16;2018:2604064. doi: 10.1155/2018/2604064. eCollection 2018.
citation: Hjorth-Hansen A, Salvesen O, Engen Hanem LG, Eggebo T, Salvesen KA, Vanky E, Odegard R. Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS. J Clin Endocrinol Metab. 2018 Feb 1;103(2):740-747. doi: 10.1210/jc.2017-01191.
citation: Christiansen SC, Vanky E, Klungland H, Stafne SN, Morkved S, Salvesen KA, Saether M, Carlsen SM. The effect of exercise and metformin treatment on circulating free DNA in pregnancy. Placenta. 2014 Dec;35(12):989-93. doi: 10.1016/j.placenta.2014.09.010. Epub 2014 Sep 23.
citation: Helseth R, Vanky E, Stridsklev S, Vogt C, Carlsen SM. Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin. Eur J Endocrinol. 2014 Apr 10;170(5):769-75. doi: 10.1530/EJE-13-0859. Print 2014 May.
citation: Carlsen SM, Martinussen MP, Vanky E. Metformin's effect on first-year weight gain: a follow-up study. Pediatrics. 2012 Nov;130(5):e1222-6. doi: 10.1542/peds.2012-0346. Epub 2012 Oct 15.