Pharmacogenetics of Metformin Action in PCOS

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00703508
First received: June 20, 2008
Last updated: May 27, 2014
Last verified: May 2014

June 20, 2008
May 27, 2014
July 2008
September 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00703508 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
Pharmacogenetics of Metformin Action in PCOS
Pharmacogenetics of Metformin Action in PCOS
  1. 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.
  2. Knowing that a specific gene predicts the effect of metformin on ovulation would facilitate more efficient and effective treatment of infertility in PCOS.

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.

Interventional
Not Provided
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Polycystic Ovary Syndrome
Drug: Metformin 500 mg tablet
Metformin 500 mg tablets; two tablets every 12 hours for 9 months
Other Name: Glucophage
Experimental: Metformin
Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration
Intervention: Drug: Metformin 500 mg tablet
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
55
March 2014
September 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Premenopausal women between 18-45 years of age and BMI less than 42
  • Diagnosed with PCOS as defined by the Rotterdam criteria, which is a combination of any two of the following three criteria: 1) chronic oligo- or amenorrhea (<8 menstrual periods annually); 2) biochemical or clinical androgen excess; and 3) polycystic ovaries on ultrasonography -Normal thyroid function tests and serum prolactin; and exclusion of 21 alpha hydroxylase deficiency by a fasting 17 alpha hydroxyprogesterone less than 200 ng/dl -In acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (CBC, SMA20,urinanalysis) -Able to provide signed, witnessed informed consent -Able to comply with study requirements

Exclusion Criteria:

-Diabetes mellitus by fasting glucose or OGTT, or clinically significant pulmonary, cardiac,renal,hepatic,neurologic,psychiatric,infectious,neoplastic and malignant disease (other than non-melanoma skin cancer) -Current use of oral contraceptives; use of fertility drugs within 6 months of study -Current or recent use (within 3 months prior to study entry) of metformin -Documented or suspected recent (within one year)history of drug abuse or alcoholism -Ingestion of any investigational drug within two months prior to study onset.

Female
18 Years to 45 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00703508
VCU IRB HM11153, 2U54HD034449
Yes
Virginia Commonwealth University
Virginia Commonwealth University
Not Provided
Principal Investigator: John E. Nestler, M.D. Virginia Commonwealth University
Virginia Commonwealth University
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP