Metabolic Syndrome in PCOS: Precursors and Interventions

Overview[ - collapse ][ - ]

Purpose 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.
ConditionPolycystic Ovary Syndrome
Metabolic Syndrome
InterventionDrug: Metformin
Drug: flutamide
Drug: drospirenone
Other: placebo
PhaseN/A
SponsorNorthwestern University
Responsible PartyNorthwestern University
ClinicalTrials.gov IdentifierNCT00442689
First ReceivedFebruary 5, 2007
Last UpdatedNovember 5, 2012
Last verifiedNovember 2012

Tracking Information[ + expand ][ + ]

First Received DateFebruary 5, 2007
Last Updated DateNovember 5, 2012
Start DateJuly 2006
Estimated Primary Completion DateNovember 2012
Current Primary Outcome MeasuresComparison of flutamide and metformin alone and in combination on cardiovascular disease risk factors after six months. [Time Frame: 6 months] [Designated as safety issue: No]
Current Secondary Outcome MeasuresPredictors of response such as baseline androgen levels, FFA levels, insulin sensitivity and genotype. [Time Frame: 6 months] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleMetabolic Syndrome in PCOS: Precursors and Interventions
Official TitleMetabolic Syndrome in PCOS: Precursors and Interventions
Brief Summary
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.
Detailed Description
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.
Study TypeInterventional
Study PhaseN/A
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Condition
  • Polycystic Ovary Syndrome
  • Metabolic Syndrome
InterventionDrug: 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.
Other Names:
  • Glucophage
  • Riomet
  • Fortamet
  • Glumetza
  • Diabex
  • Diaformin
Drug: flutamide
250 mg twice daily
Other Names:
EulexinDrug: drospirenone
one active pill per day for three weeks and then 1 sugar pill per day for one week
Other Names:
YasminOther: 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.
Other Names:
sugar pill
Study Arm (s)
  • 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

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment97
Estimated Completion DateNovember 2012
Estimated Primary Completion DateNovember 2012
Eligibility Criteria
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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00442689
Other Study ID NumbersDK73411
Has Data Monitoring CommitteeYes
Information Provided ByNorthwestern University
Study SponsorNorthwestern University
CollaboratorsNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators Principal Investigator: Andrea Dunaif, MD Northwestern University
Verification DateNovember 2012

Locations[ + expand ][ + ]

Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611