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

April 28, 2015 updated by: Kathleen M. Hoeger, MD, University of Rochester

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction in Abdominal Fat as Measured by Waist Circumference.
Time Frame: baseline and 24 weeks
Change in waist circumference measured in cms used as a measure of abdominal adiposity, pre minus post intervention
baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Weight Post Minus Pre Intervention.
Time Frame: baseline and 24 weeks
Body mass index change in adolescents enrolled in lifestyle intervention program
baseline and 24 weeks
Total Testosterone Change
Time Frame: baseline and 24 weeks
Change in total testosterone post minus pre intervention
baseline and 24 weeks
Change in Sex Hormone Binding Globulin (SHBG)
Time Frame: baseline and 24 weeks
SHBG concentration post minus pre-intervention
baseline and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rochester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

January 1, 2008

Study Completion (Actual)

January 1, 2008

Study Registration Dates

First Submitted

January 27, 2006

First Submitted That Met QC Criteria

January 27, 2006

First Posted (Estimate)

January 30, 2006

Study Record Updates

Last Update Posted (Estimate)

May 15, 2015

Last Update Submitted That Met QC Criteria

April 28, 2015

Last Verified

April 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RSRB-00012501
  • GCRC#1083

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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