Metabolic Syndrome in PCOS: Precursors and Interventions

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Andrea Dunaif, Northwestern University
ClinicalTrials.gov Identifier:
NCT00442689
First received: February 5, 2007
Last updated: November 5, 2012
Last verified: November 2012
  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.


Condition Intervention
Polycystic Ovary Syndrome
Metabolic Syndrome
Drug: Metformin
Drug: flutamide
Drug: drospirenone
Other: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Metabolic Syndrome in PCOS: Precursors and Interventions

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Comparison 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 ]

Secondary Outcome Measures:
  • Predictors of response such as baseline androgen levels, FFA levels, insulin sensitivity and genotype. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 97
Study Start Date: July 2006
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
oral contraceptive (drospirenone) plus placebo
Drug: drospirenone
one active pill per day for three weeks and then 1 sugar pill per day for one week
Other Name: Yasmin
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.
Other Name: sugar pill
Experimental: 2
Metformin plus placebo
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.
Other Names:
  • Glucophage
  • Riomet
  • Fortamet
  • Glumetza
  • Diabex
  • Diaformin
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.
Other Name: sugar pill
Experimental: 3
Flutamide plus placebo
Drug: flutamide
250 mg twice daily
Other Name: Eulexin
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.
Other Name: sugar pill
Experimental: 4
Metformin and Flutamide plus placebo
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.
Other Names:
  • Glucophage
  • Riomet
  • Fortamet
  • Glumetza
  • Diabex
  • Diaformin
Drug: flutamide
250 mg twice daily
Other Name: Eulexin
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.
Other Name: sugar pill
Placebo Comparator: 5
Placebo only
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.
Other Name: sugar pill

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00442689

Locations
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Andrea Dunaif, MD Northwestern University
  More Information

Publications:
Responsible Party: Andrea Dunaif, Charles F Kettering Professor of Endocrinology & Metabolism Vice Chair for Research, Department of Medicine Northwestern University, Feinberg School of Medicine, Northwestern University
ClinicalTrials.gov Identifier: NCT00442689     History of Changes
Other Study ID Numbers: DK73411, R01DK073411
Study First Received: February 5, 2007
Last Updated: November 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
Polycystic Ovary Syndrome
Metabolic Syndrome
PCOS
overweight
infertility
Insulin Resistance
menstrual cycle

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Metabolic Syndrome X
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Flutamide
Drospirenone
Metformin
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Hypoglycemic Agents
Aldosterone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014