Trial With Metformin in Women With Polycystic Ovary Syndrome

Polycystic Ovary Syndrome Clinical Trial

Official title:

Randomized, Cross-over Trial With Metformin in Women With Polycystic Ovary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02280057
• Other study ID #: 2166-00
• Status: Completed
• Phase: Phase 4
• First received: October 28, 2014
• Last updated: February 22, 2017
• Start date: September 2001
• Est. completion date: December 2002

Study information

• Verified date: February 2017
• Source: Herning Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators wanted to elucidate the effects of metformin in Polycystic Ovary Syndrome (PCOS) by performing a randomized, double-blinded, placebo-controlled cross-over study.

Description:

Eligible women who gave written informed consent were assigned to 6 months of treatment with either 850 mg of metformin or placebo twice daily, followed by a wash-out period of 3 months before cross-over to the alternate treatment for another 6 months. Randomization defining treatment sequence was done at inclusion by random number tables. The appearance of the tablets was identical, and patients and investigators were blinded to treatment allocation. The randomization code was stored in a closed envelope until all participants had finished the treatment. Participants were seen by one of the investigators before inclusion and every second month during treatment periods, always in the morning after an overnight fast of at least 8 h. They were weighed wearing light clothing. Waist circumference was measured at the umbilical level and hip circumference at the trochanter region. Systolic and diastolic blood pressure was measured with a semiautomatic blood pressure monitor and a blood sample was drawn for immediate analysis without respect to bleeding periods. All participants registered their bleeding periods in a calendar during both study periods and the 3 months wash-out period. Calculation of sample size was based on the assumption that at least 50% of the women would experience at least 30% more menstrual periods on metformin than on placebo. Based on a power of 90 (b = 0.10) to detect a significant difference [two-sided P-value of 0.05], the minimum sampling size was calculated to 44 subjects.

We also assumed a 10% drop-out rate, and thus aimed at including 50 women. As drop-out rate quickly rose higher than expected, we decided to include 60 women. In the intention-to-treat analysis, the values of each participant after 6 months of metformin or placebo were compared with the baseline values. Linear regression analysis with the changes in testosterone and homeostasis model assessment (HOMA) index as dependent variables was performed to examine potential relations between the changes. The per protocol analysis included data from participants completing both study periods, i.e. the difference between the values of each participant after placebo and metformin, respectively, was calculated, and a significance test performed on the differences.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: December 2002
• Est. primary completion date: December 2002
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• testosterone value above the upper normal limit and

• oligo- or amenorrhea,

Exclusion Criteria:

• periclimacteric gonadotrophin values,

• hyperprolactinaemia,

• diabetes mellitus,

• impaired thyroid,

• renal or hepatic function,

• hormonal treatment,

• pregnancy,

• lactation or a wish for fertility treatment.

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• Metformin
Metformin 1500 mg (=2 pills) per day in six months
• Placebo
2 pills per day in six months; pills look like metformin pills

Locations

Country	Name	City	State
Denmark	Gynecology Dept. Herning Hospital	Herning

Sponsors (2)

Lead Sponsor	Collaborator
Herning Hospital	GEA A/S Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (4)

Greibe E, Trolle B, Bor MV, Lauszus FF, Nexo E. Metformin lowers serum cobalamin without changing other markers of cobalamin status: a study on women with polycystic ovary syndrome. Nutrients. 2013 Jul 5;5(7):2475-82. doi: 10.3390/nu5072475. — View Citation

Madsen HN, Lauszus FF, Trolle B, Ingerslev HJ, Tørring N. Impact of metformin on anti-Müllerian hormone in women with polycystic ovary syndrome: a secondary analysis of a randomized controlled trial. Acta Obstet Gynecol Scand. 2015 May;94(5):547-51. doi: — View Citation

Trolle B, Flyvbjerg A, Kesmodel U, Lauszus FF. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. Hum Reprod. 2007 Nov;22(11):2967-73. — View Citation

Trolle B, Lauszus FF, Frystyk J, Flyvbjerg A. Adiponectin levels in women with polycystic ovary syndrome: impact of metformin treatment in a randomized controlled study. Fertil Steril. 2010 Nov;94(6):2234-8. doi: 10.1016/j.fertnstert.2010.01.057. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body weight change	Body weight changes	Six months
Primary	Testosterone (Levels of free testosterone)	Levels of free testosterone	six months
Secondary	Insulin sensitivity (measured homeostasis model assessment (HOMA) index)	Insulin sensitivity measured homeostasis model assessment (HOMA) index	Six months