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Metabolic Syndrome in PCOS: Precursors and Interventions
This study is currently recruiting participants.
Verified by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), January 2009
Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00442689
  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

Drug Information available for: Insulin Metformin Metformin hydrochloride 1,2-Dihydrospirorenone Flutamide
U.S. FDA Resources
Study Type: Interventional
Study Design: Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title: Metabolic Syndrome in PCOS: Precursors and Interventions

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

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 ]

Estimated Enrollment: 200
Study Start Date: July 2006
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
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: 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.
2: Experimental
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: 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.
3: Experimental
Flutamide plus placebo
Drug: flutamide
250 mg twice daily
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.
4: Experimental
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.
Drug: flutamide
250 mg twice daily
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.
5: Placebo Comparator
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.

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

Contacts
Contact: Andrea Dunaif, MD 312-503-2902 a-dunaif@northwestern.edu
Contact: Olga Cardenas, MD 312-503-4385 m-cardenas@md.northwestern.edu

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

Publications:
Responsible Party: Northwestern University ( Andrea Dunaif )
Study ID Numbers: DK73411
Study First Received: February 5, 2007
Last Updated: January 5, 2009
ClinicalTrials.gov Identifier: NCT00442689  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Polycystic Ovary Syndrome
Metabolic Syndrome
PCOS
overweight
infertility
Insulin Resistance
menstrual cycle

Study placed in the following topic categories:
Infertility
Gonadal Disorders
Metformin
Endocrine System Diseases
Overweight
Ovarian Diseases
Cysts
Flutamide
Insulin
Genital Diseases, Female
Polycystic Ovary Syndrome
Drospirenone
Insulin Resistance
Endocrinopathy
Ovarian Cysts

Additional relevant MeSH terms:
Neoplasms
Pathologic Processes
Disease
Aldosterone Antagonists
Hormone Antagonists
Syndrome
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Adnexal Diseases

ClinicalTrials.gov processed this record on January 16, 2009