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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
  Purpose

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.


Condition Intervention Phase
Polycystic Ovary Syndrome
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)
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Metabolic Impact of Oral Contraceptives With or Without Metformin in Obese Adolescents With Polycystic Ovary Syndrome (PCOS)

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 36
Study Start Date: January 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
metformin
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
Placebo Comparator: 0
placebo
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   12 Years to 18 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00283816

Locations
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Kathleen Hoeger, MD University of Rochester
  More Information

No publications provided

Responsible Party: Kathleen Hoeger, MD, University of Rochester Medical Center
ClinicalTrials.gov Identifier: NCT00283816     History of Changes
Other Study ID Numbers: RSRB-00012501, GCRC#1083
Study First Received: January 27, 2006
Results First Received: April 8, 2011
Last Updated: July 19, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Rochester:
Polycystic Ovary Syndrome
Overweight Adolescent Girls
Irregular Menstrual Cycles

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Syndrome
Adnexal Diseases
Cysts
Disease
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Neoplasms
Ovarian Cysts
Ovarian Diseases
Pathologic Processes
Contraceptive Agents
Contraceptives, Oral
Contraceptives, Oral, Combined
Metformin
Contraceptive Agents, Female
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014