or
forgot password

Pharmacogenetics of Metformin Action in PCOS


N/A
18 Years
45 Years
Open (Enrolling)
Female
Polycystic Ovary Syndrome

Thank you

Trial Information

Pharmacogenetics of Metformin Action 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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Outcome Time Frame:

9 months

Safety Issue:

No

Principal Investigator

John E. Nestler, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Virginia Commonwealth University

Authority:

United States: Federal Government

Study ID:

VCU IRB HM11153

NCT ID:

NCT00703508

Start Date:

July 2008

Completion Date:

March 2014

Related Keywords:

  • Polycystic Ovary Syndrome
  • PCOS
  • Polycystic Ovary Syndrome

Name

Location
Virginia Commonwealth University Richmond, Virginia  
University Of Virginia General Clinical Research Center Charlottesville, Virginia  22908