The Effects of Metformin on Pregnancy and Miscarriage Rates in Polycystic Ovary Syndrome (PCOS)
Overview[ - collapse ][ - ]
| Purpose | The purpose of this study is to determine whether metformin may improve pregnancy rates, and decrease miscarriage rates and complications of pregnancy, such as toxemia and gestational diabetes, in women with polycystic ovary syndrome (PCOS). |
|---|---|
| Condition | Polycystic Ovary Syndrome Miscarriage Infertility Toxemia Gestational Diabetes |
| Intervention | Drug: metformin |
| Phase | Phase 3 |
| Sponsor | University of Oulu |
| Responsible Party | University of Oulu |
| ClinicalTrials.gov Identifier | NCT00994812 |
| First Received | October 9, 2009 |
| Last Updated | February 22, 2010 |
| Last verified | October 2009 |
Tracking Information[ + expand ][ + ]
| First Received Date | October 9, 2009 |
|---|---|
| Last Updated Date | February 22, 2010 |
| Start Date | August 2002 |
| Estimated Primary Completion Date | December 2009 |
| Current Primary Outcome Measures | Miscarriage rates [Time Frame: at 7-8 weeks of pregnancy or later if miscarriage happens later] [Designated as safety issue: No] |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | The Effects of Metformin on Pregnancy and Miscarriage Rates in Polycystic Ovary Syndrome (PCOS) |
|---|---|
| Official Title | Effects of Metformin on Fertility and Pregnancy in Women With Polycystic Ovary Syndrome: a Randomized, Prospective, Placebo-controlled Multicenter Study |
| Brief Summary | The purpose of this study is to determine whether metformin may improve pregnancy rates, and decrease miscarriage rates and complications of pregnancy, such as toxemia and gestational diabetes, in women with polycystic ovary syndrome (PCOS). |
| Detailed Description | Women with PCOS represent about 5-10% of the general female population and one third of the women treated for infertility. Thus, the development of new therapies to improve the efficiency of ovulation induction treatments and the outcome of pregnancy, and to reduce the long-term risks of the syndrome would bring important health benefits. The central role played by insulin resistance and hyperinsulinemia in PCOS - causing hyperandrogenism, premature follicular atresia, anovulation, oligo-amenorrhea and anovulatory infertility - has led to the use of insulin-lowering drugs for the treatment of this syndrome. The most studied agent is metformin, a biguanide antihyperglycemic drug used to treat Type 2 diabetes mellitus. It has been shown to improve significantly hyperinsulinemia and insulin resistance, to decrease androgen levels, and to improve menstrual pattern and, alone or in addition to clomiphene citrate, to induce ovulation and improve pregnancy rates in women with PCOS in some studies (1,2). Metformin may also decrease risks of early spontaneous miscarriage and gestational diabetes in PCOS (3-6). Two recent RCTs, however, have shown no beneficial effect of metformin compared to placebo as regards rates of pregnancy, miscarriage or life births in women with PCOS (7,8). Our hypothesis is that metformin may improve pregnancy rates and decrease miscarriage occurrence and complications of pregnancy, such as toxemia and gestational diabetes, in women with PCOS. This multicenter randomized placebo-controlled study is conducted in all five University Hospitals of Finland (Oulu, Kuopio, Helsinki, Tampere and Turku). Blood samples are drawn and the oral glucose tolerance test (OGTT) done before and at 3 months of treatment, after which the treatment with placebo/metformin is continued another 6 months' period together with the appropriate infertility treatment. If pregnancy occurs, the OGTT is done at 7-8 weeks of pregnancy and the placebo/metformin treatment is continued until 12 weeks of pregnancy. The study has already started and is estimated to continue at least until the end of 2009. Power analysis indicated that a minimum of 60 pregnant patients are needed in each group to decrease the risk of miscarriage from 44% to the normal 15%. |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| Condition |
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| Intervention | Drug: metformin The obese women will be randomized either to metformin (2g/day) or to placebo, and the non-obese either to metformin (1.5g/day) or to placebo. All subjects will be evaluated 1 to 7 days after spontaneous menstruation (oligomenorrheic patients), or at any other convenient time (amenorrheic subjects). After the treatment of 3 months with metformin/placebo alone, another appropriate infertility treatment will be combined with metformin/placebo (clomiphene, ovulation induction, insemination or in vitro fertilization) if no pregnancy has occurred. This treatment will be continued another 6 months' period. If pregnancy occurs, subjects will be re-examined at 7-8 weeks of gestation. |
| Study Arm (s) | Experimental: Metformin |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 326 |
| Estimated Completion Date | December 2009 |
| Estimated Primary Completion Date | December 2009 |
| Eligibility Criteria | Inclusion Criteria: 1. age < 40 years at entry 2. BMI > 19 kg/m2 3. Infertility lasting > 1 year 4. Criteria for PCOS are as defined by ESHRE/ASRM: at least two of the following findings: - polycystic ovaries shown by vaginal ultrasonography (more than 12 subcapsular follicles of 3-8 mm diameter in one plane of the ovary) - oligomenorrhea or amenorrhea - clinical manifestations of hyperandrogenism such as a hirsutism score of > 7 according to Ferriman and Gallwey (Ferriman & Gallwey 1961)and/or an elevated serum testosterone level (> 2.7 nmol/l). Exclusion Criteria: 1. diabetic subjects 2. alcohol users 3. active liver disease (ALAT > +2 SD the upper normal value i.e.> 100IU/l) 4. hormonal drugs 5. past or present cardiac failure (NYHA I-IV) 6. liver or renal failure (S-Creatinine above the normal value ie.124 umol/l) 7. pregnancy or lactation 8. hypersensitivity to metformin |
| Gender | Female |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | Finland |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00994812 |
|---|---|
| Other Study ID Numbers | T59108 |
| Has Data Monitoring Committee | No |
| Information Provided By | University of Oulu |
| Study Sponsor | University of Oulu |
| Collaborators | University of Eastern Finland Helsinki University University of Tampere University of Turku |
| Investigators | Principal Investigator: Laure C Morin-Papunen, PhD University hospital of Oulu |
| Verification Date | October 2009 |
Locations[ + expand ][ + ]
| University Hospital Of Helsinki | Helsinki, Finland |
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| University Hospital of Kuopio | Kuopio, Finland |
| University Hopsital of Oulu | Oulu, Finland, 90029 |
| University Hospital of Tampere | Tampere, Finland |
| University Hospital of Turku | Turku, Finland |