Official Title: “Metabolic Syndrome in PCOS: Precursors and Interventions”

The purpose of this study is to determine whether lowering insulin levels using a medication called metformin, and blocking the action of male hormones with the medication flutamide wil decrease central body fat, improve cholesterol levels or affect sugar handling in women with PCOS (Polycystic ovary syndrome) The effects of these medications will be compared to the effects of the oral contraceptive pill (OCP), Yasmin.

Study Type: Interventional

Study Design: Other, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: January 2009

Polycystic ovary syndrome (PCOS) is one of the most common conditions of young women, and it is frequently associated with insulin resistance or metabolic syndrome (MBS). In addition, affected women have significantly elevated mean LDL levels and an increased prevalence of at risk LDL levels, independent of obesity. There is a genetic susceptibility to PCOS and we have identified a major susceptibility gene or genetic element on chromosome 19p3.2 near the insulin receptor gene that is linked and associated with the reproductive phenotype of hyperandrogenemia. We have mapped the location of this variant (allele 8[A8]D19S884)to an allele a dinucleotide repeat in intron 55 of the fibrillin 3 gene. We are directly testing the role of androgens in the metabolic abnormalities in PCOS by examining the impact of androgen receptor blockade, alone and in combination with insulin sensitization, on visceral adiposity and circulating LDL levels. Further, we will determine whether A8 is associated with differential responses to this intervention. We will use the pure antiandrogen, flutamide, and the insulin-sensitizing agent, metformin. In short term studies, OCP(oral contraceptive pill) decreased insulin sensitivity in women with PCOS. We have included a standard therapy arm with diet and the OCP, Yasmin, order to assess its impact on metabolic endpoints concurrently with the othe interventions so that the data will be directly comparable.

Intervention(s) in this Clinical Trial

• Drug: Metformin
  • 850mg tablets, 1 tablet/day with food for one week. After one week, subjects will take 1 tablet twice a day with food for the rest of the sixth month study period.
• Drug: flutamide
  • 250 mg twice daily
• Drug: drospirenone
  • one active pill per day for three weeks and then 1 sugar pill per day for one week
• Other: placebo
  • 1-3 per day for the first week and then 1-4 per day for the rest of the six month study period. Subjects may receive only placebo (arm 5) or placebo in addition to the drug(s) they receive.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • oral contraceptive (drospirenone) plus placebo
• Experimental: 2
  • Metformin plus placebo
• Experimental: 3
  • Flutamide plus placebo
• Experimental: 4
  • Metformin and Flutamide plus placebo
• Placebo Comparator: 5
  • Placebo only

Primary Measures

• Comparison of flutamide and metformin alone and in combination on cardiovascular disease risk factors after six months.
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• Predictors of response such as baseline androgen levels, FFA levels, insulin sensitivity and genotype.
  • Time Frame: 6 months
    Safety Issue?: No

Inclusion Criteria:

• 6 periods or fewer per year
• Overweight
• All ethnicities

Exclusion Criteria:

• Diabetes
• Heart Disease
• Chronic illness
• Regular Smokers
• Current use of Birth Control Pills, Patch, Ring, Depo

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 35 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Overall Clinical Trial Officials and Contacts

Andrea Dunaif, MD Principal Investigator Northwestern University  

Overall Contact: Andrea Dunaif, MD 312-503-2902 a-dunaif@northwestern.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00442689

Study ID Number: DK73411

ClinicalTrials.gov Identifier: NCT00442689

Health Authority: United States: Food and Drug Administration