Androgen Excess as a Mechanism for Adipogenic Dysfunction in PCOS Women
The purpose of this research study is to collect specimen samples and study medical information from women with Polycystic Ovary Syndrome (PCOS) and women without PCOS. The goal is to learn more about the changes that take place in the body that result in PCOS.
We anticipate that 59 women will take part in this study (15 without PCOS and 44 with PCOS). All patients will undergo a physical exam, blood tests, and ultrasound of their ovaries. If they meet the criteria for this study, they will then undergo additional blood tests, removal of a small amount of subcutaneous abdominal fat, measurement of regional body fat (i.e., MRI, DXA scan), a modified frequently-sampled intravenous glucose tolerance test (FSIGTT), and determination of ovarian function (via a follicle stimulating hormone [FSH] test). The women without PCOS will be complete the study at this point.
The women with PCOS will be randomized to receive the drug flutamide 125 mg/day or placebo. They will take the drug every day for six 28-day cycles. They will be asked to collect and store a urine sample once a week. They will also be asked to complete a pill diary and menstrual diary. Once a month while they are taking the flutamide/placebo, they will return to the clinic and bring their frozen urine samples. At that time they will undergo a physical exam, toxicity assessment, and blood draw.
Quality of Life assessments will be done at the beginning of the study for all participants. Women with PCOS who are taking the flutamide or placebo will be asked to repeat the Quality of Life assessments during the study and at the end of the study.
Six months following the completion of protocol procedures, participants who received flutamide/placebo will be contacted by phone to check on the status of their health. They will be asked if they have experienced any health problems or have become pregnant since they completed the study procedures.
After the six 28-day cycles are completed they will then undergo additional blood tests, removal of a small amount of subcutaneous abdominal fat, measurement of regional body fat (i.e., MRI, DXA scan), a modified frequently-sampled intravenous glucose tolerance test (FSIGTT), and determination of ovarian function (via a FSH test).
|Polycystic Ovary Syndrome (PCOS)||Drug: Flutamide Other: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Androgen Excess as a Mechanism for Adipogenic Dysfunction in PCOS Women|
- Six-month flutamide (antiandrogen) administration to lean women with polycystic ovary syndrome (PCOS) will improve impaired glucose tolerance by glucose tolerance testing and normalize the size of enlarged subcutaneous (SC) fat cells by fat biopsy. [ Time Frame: 6 months ]Women with PCOS exhibit impaired glucose tolerance that correlates with enlarged subcutaneous (SC) abdominal adipocytes. Since a common denominator to these abnormalities is hyperandrogenism, we hypothesize that 6-month flutamide (antiandrogen) administration to lean PCOS women will improve glucose tolerance by glucose tolerance testing and reduce subcutaneous (SC) abdominal adipocyte size, as determined by SC abdominal fat biopsy.
- Six-month flutamide (antiandrogen) administration to lean women with polycystic ovary syndrome (PCOS) will establish ovulatory menstrual cycles, as determined by menstrual diaries and weekly urinary progesterone (metabolite) determinations. [ Time Frame: 6 months ]Women with PCOS exhibit oligo-ovulation, in part due to hyperandrogenism. We hypothesize that 6-month flutamide (antiandrogen) administration to lean PCOS women will establish ovulatory menstrual cycles, as determined by menstrual diaries and weekly urinary progesterone (metabolite) determinations.
- Quality of Life Questionnaires [ Time Frame: 6 months ]
- Liver transaminases (serum glutamic oxaloacetic transaminase [SGOT]; serum glutamic-pyruvic transaminase [SGPT]) [ Time Frame: 6 months ]This study carefully considers the safety of low-dose flutamide in examining how hyperandrogenism in PCOS affects ovarian function, subcutaneous fat storage and glucose metabolism. The 125 mg oral dose of flutamide has been specifically chosen because it has not been associated with liver enzyme abnormalities (0%, 62.5-125 mg/day), while being as effective as high dose flutamide in improving androgenic symptoms. Furthermore, in the rare event mild elevation of hepatic enzymes occurs with low-dose flutamide despite its dose-dependency, it is easily detected and reversible.
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||March 2018|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
Placebo Comparator: Sugar pill
Placebo orally each 28 day cycle for 6 cycles
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide 25 mg orally each 28 day cycle for 6 cycles
Other Name: Euflex
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01889199
|Contact: Daniel A Dumesic, MD||(310) 794-5542||DDumesic@mednet.ucla.edu|
|Contact: Andrea Rapkin, MD||(310) 825-6301||ARapkin@mednet.ucla.edu|
|United States, California|
|Los Angeles, California, United States, 90095-1740|
|Contact: Daniel A Dumesic, MD 310-794-5542 DDumesic@mednet.ucla.edu|
|Contact: Rapkin Andrea, MD (310) 825-6301 ARapkin@mednet.ucla.edu|
|Principal Investigator:||Daniel Dumesic, MD||University of California, Los Angeles|