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: May 9, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to investigate the metabolic effects of anti-androgens and oral contraceptive pills (OCPs), compared with placebo, in the treatment of women with PCOS. We hypothesized that controlling elevated androgen levels with either anti-androgens or OCPs would produce improvement in metabolic markers in PCOS women and would reduce their long term metabolic risk.


Condition Intervention
Polycystic Ovary Syndrome
Metabolic Syndrome
Drug: flutamide
Drug: ethinyl estradiol 35 mcg and drospirenone 3 mg
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:
  • Change in Low-density Lipoprotein (LDL) Levels Over the Study Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in low-density lipoprotein (LDL) levels over the study period (LDL level at study endpoint - baseline LDL level)

  • Change in High-density Lipoprotein (HDL) Levels During Study Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in high-density lipoprotein (HDL) levels during study period (HDL level at study endpoint - baseline HDL)

  • Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in visceral adipose tissue (VAT) volume as measured by MRI (VAT at study endpoint - baseline VAT)

  • Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in fat percentage as measured by DEXA scan over the study period (Fat percentage at study endpoint - baseline fat percentage)

  • Change in Disposition Index [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in disposition index (DI, insulin secretion corrected for insulin secretion) as measured by frequently-sampled IV glucose tolerance test (DI at study endpoint - baseline DI)

  • Change in Resting Energy Expenditure (REE) Over the Study Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in resting energy expenditure (REE) over the study period (REE at study endpoint - baseline REE)

  • Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in maximal aerobic exercise capacity (VO2 max) over the study period (VO2 max at study endpoint - baseline VO2 max)


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 (35 mg ethinyl estradiol)
Drug: ethinyl estradiol 35 mcg and drospirenone 3 mg
one active pill per day for three weeks and then 1 sugar pill per day for one week
Other Name: Yasmin
Experimental: 2
Flutamide 250 mg twice daily
Drug: flutamide
250 mg twice daily
Other Name: Eulexin
Placebo Comparator: 3
Placebo
Other: placebo
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 low-density lipoprotein (LDL) levels and an increased prevalence of at risk LDL levels, independent of obesity. We are directly testing the role of androgens in the metabolic abnormalities in PCOS by examining the impact of direct androgen receptor blockade by anti-androgen medications and indirect suppression of androgen production through suppression of leutinizing hormone (LH) with oral contraceptive pills (OCPs), compared with placebo, on visceral adiposity, circulating LDL levels, insulin secretion and sensitivity as measured by frequently-sampled IV glucose tolerance tests (FSIGT) and oral glucose tolerance tests (OGTT), resting energy expenditure, and maximal aerobic capacity measurement.

Note: Originally there were 2 additional study arm, Metformin only and Metformin + Flutamide. These study arms were ultimately eliminated and were not included in analysis of baseline characteristics or endpoints.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Results First Received: April 9, 2014
Last Updated: May 9, 2014
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
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Flutamide
Drospirenone
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 15, 2014