Clinical trial NCT00442689: Metabolic Syndrome in PCOS: Precursors and Interventions
Official title: Metabolic Syndrome in PCOS: Precursors and Interventions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Metabolic Syndrome
Keywords: Polycystic Ovary Syndrome
Metabolic Syndrome
PCOS
overweight
infertility
Insulin Resistance
menstrual cycle
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2007-03-02
Enrollment: 97
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.

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 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

Primary outcomes:
measure: Change in Low-density Lipoprotein (LDL) Levels Over the Study Period
timeFrame: 6 months
measure: Change in High-density Lipoprotein (HDL) Levels During Study Period
timeFrame: 6 months
measure: Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI
timeFrame: 6 months
measure: Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period
timeFrame: 6 months
measure: Change in Disposition Index
timeFrame: 6 months
measure: Change in Resting Energy Expenditure (REE) Over the Study Period
timeFrame: 6 months
measure: Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Northwestern University
name: Andrea Dunaif, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1210/jcem.83.8.5041.
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. doi: 10.1210/jc.2005-2250. Epub 2006 Jul 25.
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. doi: 10.1111/j.1365-2265.2004.01973.x.
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. doi: 10.1210/jc.2007-0761. Epub 2007 Sep 4.