Metabolic Syndrome in PCOS: Precursors and Interventions

• ClinicalTrials.gov Identifier: NCT00442689
• Recruitment Status: Completed
• First Posted: March 2, 2007
• Results First Posted: June 6, 2014
• Last Update Posted: June 6, 2014
• Sponsor: Northwestern University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Andrea Dunaif, Northwestern University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Polycystic Ovary Syndrome; Metabolic Syndrome	Drug: flutamide; Drug: ethinyl estradiol 35 mcg and drospirenone 3 mg; Other: placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Official Title: Metabolic Syndrome in PCOS: Precursors and Interventions
• Study Start Date: July 2006
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: November 2012

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Change in Low-density Lipoprotein (LDL) Levels Over the Study Period [ Time Frame: 6 months ]
   Change in low-density lipoprotein (LDL) levels over the study period (LDL level at study endpoint - baseline LDL level)
2. Change in High-density Lipoprotein (HDL) Levels During Study Period [ Time Frame: 6 months ]
   Change in high-density lipoprotein (HDL) levels during study period (HDL level at study endpoint - baseline HDL)
3. Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI [ Time Frame: 6 months ]
   Change in visceral adipose tissue (VAT) volume as measured by MRI (VAT at study endpoint - baseline VAT)
4. Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period [ Time Frame: 6 months ]
   Change in fat percentage as measured by DEXA scan over the study period (Fat percentage at study endpoint - baseline fat percentage)
5. Change in Disposition Index [ Time Frame: 6 months ]
   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. Change in Resting Energy Expenditure (REE) Over the Study Period [ Time Frame: 6 months ]
   Change in resting energy expenditure (REE) over the study period (REE at study endpoint - baseline REE)
7. Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period [ Time Frame: 6 months ]
   Change in maximal aerobic exercise capacity (VO2 max) over the study period (VO2 max at study endpoint - baseline VO2 max)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes 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

Locations

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Andrea Dunaif, MD; Northwestern University

More Information

Publications:

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.

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.

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.

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.

• 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
• Other Study ID Numbers: DK73411; R01DK073411 ( U.S. NIH Grant/Contract )
• First Posted: March 2, 2007
• Results First Posted: June 6, 2014
• Last Update Posted: June 6, 2014
• Last Verified: May 2014

Keywords provided by Andrea Dunaif, Northwestern University:

Polycystic Ovary Syndrome; Metabolic Syndrome; PCOS; overweight; infertility; Insulin Resistance; menstrual cycle

Additional relevant MeSH terms:

Polycystic Ovary Syndrome; Metabolic Syndrome; Syndrome; Disease; Pathologic Processes; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine System Diseases; Flutamide; Drospirenone; Ethinyl Estradiol; Estradiol; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Contraceptives, Oral