Pharmacogenetics of Metformin Action in PCOS
- The polycystic ovary syndrome is the major cause of infertility in the United States. Metformin has been shown to increase frequency of ovulations in PCOS, and is used in clinical practice to treat infertility, but some women with PCOS do not respond to metformin treatment.
- Knowing that a specific gene predicts the effect of metformin on ovulation would facilitate more efficient and effective treatment of infertility in PCOS.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacogenetics of Metformin Action in PCOS|
- Determine if ovulations/9months/woman is greater in women with the G/G genotype of STK11 rs8111699 compared with women with the C/G and C/C genotypes. [ Time Frame: 9 months ] [ Designated as safety issue: No ]
- Determine in which genotype(s) frequency of ovulation correlates with improvement in insulin sensitivity and/or reduction in total testosterone. [ Time Frame: 9 months ] [ Designated as safety issue: No ]
|Study Start Date:||July 2008|
|Study Completion Date:||March 2014|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration
Drug: Metformin 500 mg tablet
Metformin 500 mg tablets; two tablets every 12 hours for 9 months
Other Name: Glucophage
The polycystic ovary syndrome (PCOS) affects approximately 6-10% of women of childbearing age, i.e., 3.5-5.5 million women in the United States. PCOS is the most common endocrine disturbance of young women and the major cause (75%) of anovulatory infertility in the United States. We hypothesize that women with the polycystic ovary syndrome (PCOS) who have the G/G genotype of single nucleotide polymorphism (SNP)_ rs8111699 in STK11 will exhibit a significantly greater response to metformin, in terms of ovulation, compared with women with either the C/G or C/C genotype. Specifically, we anticipate the frequency of ovulation (defined by number of ovulations/9 months/subject) to be at least 2-fold higher in women with the G/G STK11 genotype compared with women with either the C/G or C/C genotype.
To test this hypothesis, we will obtain DNA for STK11 genotyping in 36 women with PCOS who are treated with metformin and carefully monitored for ovulation for 9 months. STK11 genotype status will be determined, and the ovulation rates in the G/G, G/C and C/C genotype groups will be compared with one another. Our goal is to identify the genes that predict or modify response to commonly prescribed medications that will allow physicians to better choose among existing therapies and individualize treatment. While metformin has been shown to increase ovulatory frequency in PCOS and is widely used in clinical practice to treat infertility, a substantial number of women either do not respond or are slow to respond to metformin treatment.
Knowing that a specific STK11 genotype predicts the effect of metformin on ovulation would facilitate more efficient and effective treatment of infertility in PCOS.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00703508
|United States, Virginia|
|University Of Virginia General Clinical Research Center|
|Charlottesville, Virginia, United States, 22908|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||John E. Nestler, M.D.||Virginia Commonwealth University|