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Impact of Metformin in Teens With Polycystic Ovary Syndrome (PCOS) on Oral Contraceptive Therapy

This study has been completed.
Sponsor:
Information provided by:
University of Rochester
ClinicalTrials.gov Identifier:
NCT00283816
First received: January 27, 2006
Last updated: July 19, 2011
Last verified: April 2011

January 27, 2006
July 19, 2011
January 2006
January 2008   (final data collection date for primary outcome measure)
Reduction in Abdominal Fat as Measured by Waist Circumference. [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]
Change in waist circumference measured in cms used as a measure of abdominal adiposity, pre minus post intervention
24 week trial to compare effect of metformin to placebo, in combination with oral contraceptives with respect to change in metabolic parameters of increased cardiovascular risk and insulin resistance.
Complete list of historical versions of study NCT00283816 on ClinicalTrials.gov Archive Site
  • Change in Weight Post Minus Pre Intervention. [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]
    Body mass index change in adolescents enrolled in lifestyle intervention program
  • Total Testosterone Change [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]
    Change in total testosterone post minus pre intervention
  • Change in Sex Hormone Binding Globulin (SHBG) [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]
    SHBG concentration post minus pre-intervention
Assess the effectiveness & impact of a lifestyle management program in combination with oral contraceptives +/- metformin in producing weigh reduction and improvement in fitness capacity in obese adolescents with PCOS.
Not Provided
Not Provided
 
Impact of Metformin in Teens With Polycystic Ovary Syndrome (PCOS) on Oral Contraceptive Therapy
Metabolic Impact of Oral Contraceptives With or Without Metformin in Obese Adolescents With Polycystic Ovary Syndrome (PCOS)

Oral contraceptives are known to improve menstrual cycles and symptoms in PCOS, however may increase cholesterol. Metformin, a drug to improve insulin resistance, may benefit metabolic state. This study is to determine whether metformin added to oral contraceptive therapy in adolescent women with PCOS improves metabolic state.The study will also test a lifestyle improvement program to reduce weight.

Polycystic Ovary Syndrome (PCOS) is a heterogeneous condition characterized by chronic anovulation and androgen excess that occurs in 4-8% of unselected adult women. Although signs and symptoms of the disorder typically appear at the time of puberty, diagnosis is often delayed until adulthood. At least 50% of adult women with PCOS are obese, resulting in a more severe clinical picture. Obesity among adolescents has been increasing in recent years, with overrepresentation of females who show evidence of hyperandrogenism and irregular periods, suggesting an association of obesity and PCOS at an early age. Recent data, however, have drawn attention to the long-term risks of PCOS, including diabetes and cardiovascular disease. Insulin resistance plays a critical role in the pathophysiology of PCOS and is thought to be the metabolic abnormality most closely linked to an increased risk of diabetes and heart disease. Traditional treatments with oral contraceptives are associated with reduction in serum androgens and improvements in menstrual cycles in adolescents with PCOS, however these have not been well-studied in obese adolescents. Oral contraceptives may worsen the dyslipidemia seen in obese women with PCOS and do not address the insulin resistance. Metformin, an insulin sensitizing agent, has been shown to improve metabolic features of PCOS, but combination therapy with oral contraceptives has never been studied in the obese adolescent with PCOS.

The major hypothesis of this proposal is that metformin will improve the metabolic profile of obese adolescent girls with PCOS treated with oral contraceptives. Additionally, a secondary hypothesis will be that compliance with a concurrent lifestyle modification program with be associated with the most significant improvements.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Polycystic Ovary Syndrome
  • Drug: Metformin
    Metformin 500 mg. tabs 2 tabs BID for duration of study
    Other Names:
    • Metformin Hydrochloride Tablets, 500 mg.
    • manufacturer: Mylan Pharmaceuticals, Morgantown, WV
  • Drug: Oral Contraceptive Pill

    Yasmin, drospirenone and ethinyl estradiol 28 tablets

    1 tab daily for duration of study

    Other Names:
    • Yasmin 28 tablets
    • Manufacturer: Berlex, Montville, NJ 07045
  • Behavioral: Lifestyle Management Program
    Subjects and a parent/guardian will participate in a series of classes for training in diet, exercise & behavior modification skills on a regular weekly basis over the 24 week study
  • Behavioral: Quality of Life Questionnaire
    Quality of Life questionnaire designed for women with Polycystic Ovary Syndrome. Questions concern health and health related issues Performed twice during study, at baseline and conclusion
  • Procedure: Oral Glucose Tolerance Test

    Insulin response to a glucose challenge in an oral glucose tolerance test (OGTT), as measured by area under the curve (AUC). In this study we will administer an OGTT and calculate the AUC as a measure of insulin resistance.

    Performed twice during study, at baseline and conclusion

  • Procedure: Blood work
    Initial and conclusion blood draws include; comprehensive metabolic profile, CBC and platelet,hormonal assessment and lipids.
  • Procedure: Abdominal Ultra Sound

    transabdominal transducer, which contains integrated software for volume calculation will be used to assess ovarian volume.

    Performed twice during study, at baseline and conclusion

  • Procedure: Dual-energy x-ray absorptiometry (DEXA scan)
    Dual-energy x-ray absorptiometry (DEXA) will be used to assess percent body fat Performed twice during study, at baseline and conclusion
  • Drug: placebo
    placebo capsules, two capsules BID
    Other Names:
    • placebo formulation: 240 mg. lactose powder USP
    • in size 3 capsules from Capsugel
  • Active Comparator: 1
    metformin
    Interventions:
    • Drug: Metformin
    • Drug: Oral Contraceptive Pill
    • Behavioral: Lifestyle Management Program
    • Behavioral: Quality of Life Questionnaire
    • Procedure: Oral Glucose Tolerance Test
    • Procedure: Blood work
    • Procedure: Abdominal Ultra Sound
    • Procedure: Dual-energy x-ray absorptiometry (DEXA scan)
  • Placebo Comparator: 0
    placebo
    Interventions:
    • Drug: Oral Contraceptive Pill
    • Behavioral: Lifestyle Management Program
    • Behavioral: Quality of Life Questionnaire
    • Procedure: Oral Glucose Tolerance Test
    • Procedure: Blood work
    • Procedure: Abdominal Ultra Sound
    • Procedure: Dual-energy x-ray absorptiometry (DEXA scan)
    • Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
January 2008
January 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:Age 12-18 years; Menstrual irregularity; Overweight; Must be able to swallow capsules; At lease 6 months since onset of first menstrual cycle.

Exclusion Criteria:Diabetes; Kidney or Liver disease; Tobacco use; Depression or Bipolar Disease; Contraindication to exercise; Weight > 300 lbs.

Female
12 Years to 18 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00283816
RSRB-00012501, GCRC#1083
Yes
Kathleen Hoeger, MD, University of Rochester Medical Center
University of Rochester
Not Provided
Principal Investigator: Kathleen Hoeger, MD University of Rochester
University of Rochester
April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP