Metabolic Syndrome in PCOS: Precursors and Interventions

Metabolic Syndrome Clinical Trial

Official title:

Metabolic Syndrome in PCOS: Precursors and Interventions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00442689
• Other study ID #: DK73411
• Secondary ID: R01DK073411
• Status: Completed
• Phase: N/A
• First received: February 5, 2007
• Last updated: May 9, 2014
• Start date: July 2006
• Est. completion date: November 2012

Study information

• Verified date: May 2014
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• flutamide
250 mg twice daily
• 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:
• placebo

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Diamanti-Kandarakis E, Mitrakou A, Raptis S, Tolis G, Duleba AJ. The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1998 Aug;83(8):2699-705. — View Citation

Gambineri A, Patton L, Vaccina A, Cacciari M, Morselli-Labate AM, Cavazza C, Pagotto U, Pasquali R. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. J Clin Endocrinol Metab. 2006 Oct;91(10):3970-80. Epub 2006 Jul 25. — View Citation

Gambineri A, Pelusi C, Genghini S, Morselli-Labate AM, Cacciari M, Pagotto U, Pasquali R. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2004 Feb;60(2):241-9. — View Citation

Urbanek M, Sam S, Legro RS, Dunaif A. Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype. J Clin Endocrinol Metab. 2007 Nov;92(11):4191-8. Epub 2007 Sep 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Low-density Lipoprotein (LDL) Levels Over the Study Period	Change in low-density lipoprotein (LDL) levels over the study period (LDL level at study endpoint - baseline LDL level)	6 months	No
Primary	Change in High-density Lipoprotein (HDL) Levels During Study Period	Change in high-density lipoprotein (HDL) levels during study period (HDL level at study endpoint - baseline HDL)	6 months	No
Primary	Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI	Change in visceral adipose tissue (VAT) volume as measured by MRI (VAT at study endpoint - baseline VAT)	6 months	No
Primary	Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period	Change in fat percentage as measured by DEXA scan over the study period (Fat percentage at study endpoint - baseline fat percentage)	6 months	No
Primary	Change in Disposition Index	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)	6 months	No
Primary	Change in Resting Energy Expenditure (REE) Over the Study Period	Change in resting energy expenditure (REE) over the study period (REE at study endpoint - baseline REE)	6 months	No
Primary	Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period	Change in maximal aerobic exercise capacity (VO2 max) over the study period (VO2 max at study endpoint - baseline VO2 max)	6 months	No