Pharmacogenetics of Metformin Action in PCOS

NCT ID: NCT00703508

Last Updated: 2017-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2014-03-31

Brief Summary

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.

Detailed Description

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.

Conditions

Polycystic Ovary Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin

Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration

Group Type: EXPERIMENTAL

Metformin 500 mg tablet

Intervention Type: DRUG

Metformin 500 mg tablets; two tablets every 12 hours for 9 months

Interventions

Metformin 500 mg tablet

Metformin 500 mg tablets; two tablets every 12 hours for 9 months

Intervention Type: DRUG

Other Intervention Names

Glucophage

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John E. Nestler, M.D.

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

University Of Virginia General Clinical Research Center

Charlottesville, Virginia, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

References

Cheang KI, Bhavi Modi, Maria Shulleeta, William S. Evans, Lubna Pal, Jerome F. Strauss and John E. Nestler: Genetic Polymorphisms and Ovulatory Responsiveness to Metformin in Women with Polycystic Ovary Syndrome. Endo Reviews 36 (2): Supplement THR-109, Apr. 2015.

Reference Type: RESULT

Related Links

http://www.vcu.edu/pcos

Related Info

Other Identifiers

2U54HD034449

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HM11153

Identifier Type: -

Identifier Source: org_study_id