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

NCT ID: NCT00283816

Last Updated: 2015-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2008-01-31

Brief Summary

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.

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.

Conditions

Polycystic Ovary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

metformin

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin 500 mg. tabs 2 tabs BID for duration of study

Oral Contraceptive Pill

Intervention Type: DRUG

Yasmin, drospirenone and ethinyl estradiol 28 tablets

1 tab daily for duration of study

Lifestyle Management Program

Intervention Type: BEHAVIORAL

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

Quality of Life Questionnaire

Intervention Type: BEHAVIORAL

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

Oral Glucose Tolerance Test

Intervention Type: PROCEDURE

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

Blood work

Intervention Type: PROCEDURE

Initial and conclusion blood draws include; comprehensive metabolic profile, CBC and platelet,hormonal assessment and lipids.

Abdominal Ultra Sound

Intervention Type: PROCEDURE

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

Performed twice during study, at baseline and conclusion

Dual-energy x-ray absorptiometry (DEXA scan)

Intervention Type: PROCEDURE

Dual-energy x-ray absorptiometry (DEXA) will be used to assess percent body fat Performed twice during study, at baseline and conclusion

0

placebo

Group Type: PLACEBO_COMPARATOR

Oral Contraceptive Pill

Intervention Type: DRUG

Yasmin, drospirenone and ethinyl estradiol 28 tablets

1 tab daily for duration of study

Lifestyle Management Program

Intervention Type: BEHAVIORAL

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

Quality of Life Questionnaire

Intervention Type: BEHAVIORAL

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

Oral Glucose Tolerance Test

Intervention Type: PROCEDURE

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

Blood work

Intervention Type: PROCEDURE

Initial and conclusion blood draws include; comprehensive metabolic profile, CBC and platelet,hormonal assessment and lipids.

Abdominal Ultra Sound

Intervention Type: PROCEDURE

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

Performed twice during study, at baseline and conclusion

Dual-energy x-ray absorptiometry (DEXA scan)

Intervention Type: PROCEDURE

Dual-energy x-ray absorptiometry (DEXA) will be used to assess percent body fat Performed twice during study, at baseline and conclusion

placebo

Intervention Type: DRUG

placebo capsules, two capsules BID

Interventions

Metformin

Metformin 500 mg. tabs 2 tabs BID for duration of study

Intervention Type: DRUG

Oral Contraceptive Pill

Yasmin, drospirenone and ethinyl estradiol 28 tablets

1 tab daily for duration of study

Intervention Type: DRUG

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

Intervention Type: 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

Intervention Type: BEHAVIORAL

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

Intervention Type: PROCEDURE

Blood work

Initial and conclusion blood draws include; comprehensive metabolic profile, CBC and platelet,hormonal assessment and lipids.

Intervention Type: 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

Intervention Type: 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

Intervention Type: PROCEDURE

placebo

placebo capsules, two capsules BID

Intervention Type: DRUG

Other Intervention Names

Metformin Hydrochloride Tablets, 500 mg.; manufacturer: Mylan Pharmaceuticals, Morgantown, WV; Yasmin 28 tablets; Manufacturer: Berlex, Montville, NJ 07045; placebo formulation: 240 mg. lactose powder USP; in size 3 capsules from Capsugel

Eligibility Criteria

Inclusion 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Kathleen M. Hoeger, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kathleen Hoeger, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of Rochester Medical Center

Rochester, New York, United States

Countries

United States

Other Identifiers

GCRC#1083

Identifier Type: -

Identifier Source: secondary_id

RSRB-00012501

Identifier Type: -

Identifier Source: org_study_id