Treatment of Adolescent Polycystic Ovary Syndrome (PCOS)

Study Overview
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Brief Summary
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A 24 week study to compare the use of Metformin, birth control pills and a carefully planned intensive lifestyle program that includes weight loss and exercise. These approaches will be compared to placebo (a pill that contains no active substances. Metformin, birth control pills and the lifestyle management program will be used on this research study to compare their ability to: reduce fasting glucose levels reduce androgen hormone levels improve sex steroid binding, and improve lipids (fatty substances in the blood)

Detailed Description
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Polycystic ovary syndrome (PCOS) is a condition associated with irregular menstrual cycles, (due to lack of regular ovulation), and evidence of elevated androgen (male hormone) levels, such as unwanted hair growth or acne. This condition often becomes recognized at the time of puberty. The standard treatment for this condition is oral contraceptive pills, which are used not for contraception, but to cause a regular, monthly bleeding pattern. Many adolescents with PCOS have increased levels of insulin, a hormone that controls the body's sugar balance. These increased insulin levels may play a role in the development of polycystic ovary syndrome. There are several medications now available, which can decrease the insulin levels by improving the action of insulin in the body. Metformin is one of these drugs. Metformin is a drug currently used in the management of diabetes to control blood sugar. It is hoped that by lowering the insulin levels some of the symptoms of polycystic ovary syndrome, such as the lack of regular periods and unwanted hair growth, can be reversed or diminished.

Official Title
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Treatment of Polycystic Ovary Syndrome (POS) in Overweight Adolescents

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin
* Drug: Oral Contraceptive Pills (Yasmin)
* Behavioral: Lifestyle Modification
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Menstrual irregularity defined as cycle length > 45 days Overweight as BMI > 25 Clinical evidence of hirsuitism or acne Testosterone > 50ng/dL Exclusion Criteria: History of diabetes mellitus History of Cushing's disease History of hyperprolactinemia Untreated hypo or hyperthyroidism History of adrenal hyperplasia Significant renal impairment Received oral contraceptives, estrogen or progestin or other drugs known to effect lipoprotein metabolism within 2 months of starting the study Exercise > 10 hours per week

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Metformin | Drug: Metformin<br>* Metformin 425mg. capsules, 2 capsules BID x 24 weeks<br>|
| Experimental: 2<br>Oral Contraceptive Pills | Drug: Oral Contraceptive Pills (Yasmin)<br>* Yasmin oral contraceptive tabs; 1 tab daily x 24 weeks<br>* Other names: Yasmin oral COntraceptive tabs;|
| Active Comparator: 3<br>lifestyle modification program | Behavioral: Lifestyle Modification<br>* weekly classes x 24 weeks for training in diet, exercise and behavior modification skills<br>|
| Placebo Comparator: 4<br>placebo to active metformin arm | Drug: placebo<br>* placebo to the active metformin arm. 2 capsules BID x 24 weeks.<br>* Other names: pharmacy matched placebo capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Number of Adolescent Girls With PCOS Who Can be Successfully Recruited Into a Randomized Clinical Trial That Includes Lifestyle Modification | The measure is to determine a number of successfully recruited overweight or obese adolescents to a randomized trial of lifestyle therapy in the community of Rochester, NY | 24 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight Loss in Lifestyle Intervention Group | In the adolescent women assigned to the lifestyle program, did the intervention program obtain weight reduction as measured by change in BMI | baseline and 24 weeks | 
| Change in Free Androgen Index (FAI) | Secondary measures of reduction in androgen measures of the different treatment arms. This is a ratio of total testosterone to sex hormone binding globulin (SHBG). The lower values correlate with lower amount of free testosterone. FAI <4 is consistent with a normal range. | baseline and 24 weeks | 
| Change in SHBG | Measurement of SHBG by treatment group pre and post intervention | baseline and 24 weeks | 
| Triglyceride Concentration by Treatment Group | Change in triglyceride measures pre and post intervention as representative of lipid changes by treatment group; metformin, lifestyle intervention, oral contraceptive or placebo | baseline and 24 weeks | 
| Change in Fasting Glucose | Change in fasting glucose concentration by treatment group pre to post intervention | baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic Ovary Syndrome, Overweight Adolescent Girls, Irregular Menstrual Cycles