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

Polycystic Ovary Syndrome Clinical Trial

Official title:

Metabolic Impact of Oral Contraceptives With or Without Metformin in Obese Adolescents With Polycystic Ovary Syndrome (PCOS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00283816
• Other study ID #: RSRB-00012501
• Secondary ID: GCRC#1083
• Status: Completed
• Phase: Phase 3
• First received: January 27, 2006
• Last updated: April 28, 2015
• Start date: January 2006
• Est. completion date: January 2008

Study information

• Verified date: April 2011
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 12 Years to 18 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• Metformin
Metformin 500 mg. tabs 2 tabs BID for duration of study
• Oral Contraceptive Pill
Yasmin, drospirenone and ethinyl estradiol 28 tablets 1 tab daily for duration of study

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

Locations

Country	Name	City	State
United States	University of Rochester Medical Center	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in Abdominal Fat as Measured by Waist Circumference.	Change in waist circumference measured in cms used as a measure of abdominal adiposity, pre minus post intervention	baseline and 24 weeks	No
Secondary	Change in Weight Post Minus Pre Intervention.	Body mass index change in adolescents enrolled in lifestyle intervention program	baseline and 24 weeks	No
Secondary	Total Testosterone Change	Change in total testosterone post minus pre intervention	baseline and 24 weeks	No
Secondary	Change in Sex Hormone Binding Globulin (SHBG)	SHBG concentration post minus pre-intervention	baseline and 24 weeks	No