Insulin Resistance, Polycystic Ovary Syndrome, and Bone Research Study

Obesity, Insulin Resistance, and Bone Metabolism in Adolescents With PCOS: Effects of Insulin Sensitizers Versus Oral Contraceptives

The purpose is to investigate the effects of 2 different treatments (drospirenone/ethinyl estradiol versus rosiglitazone) on insulin sensitivity and androgen levels, inflammatory markers, vascular markers and bone development in overweight adolescent females with polycystic ovary syndrome (PCOS).

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: rosiglitazone; Drug: drospirenone/ethinyl estradiol

Detailed Description

The purpose of this study is to:

1) to compare effects of treatment with drospirenone/ethinyl estradiol (Yasmin)versus rosiglitazone (Avandia) on hyperandrogenism, insulin resistance/hyperinsulinemia, adrenal hyperresponsiveness, body composition, chronic inflammation, bone mass and turnover.

OCPs are the first-line therapy for PCOS, however, they do not address the insulin resistance or the inflammation. Insulin sensitizers have been used successfully to treat PCOS but thiazolidinediones such as rosiglitazone have not been used in adolescents. Therefore we will investigate the effects of treatment with drospirenone/ethinyl estradiol versus rosiglitazone in overweight adolescents with PCOS. We will obtain comprehensive evaluations before and 6 months after randomization, to the respective treatment arms to determine the differences between the 2 treatment modalities.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age 10 - 20 years
• Pubertal level of Tanner stage III-V and menarchal
• BMI percentile for age and sex greater than or equal to 85%ile

Exclusion Criteria:

• Oral medications for PCOS, or that have impact on bone (i.e. anti-epileptics)
• Presence of other diseases, systemic or psychiatric, or chronic medications which could interfere with endocrine function
• Established diagnosis of diabetes
• Prior bone surgery, prior osteoporotic fracture, or fracture in the past 12 months
• Prior thromboembolic event, such as a deep venous thrombosis or pulmonary embolism (PCOS subjects only)
• Vitamin D deficiency (<10ng/mL)
• Hyperkalemia (K>5.0 meq/L)
• Positive pregnancy test (serum)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rosiglitazone; Treatment naive overweight adolescent females with PCOS treated with Rosiglitazone	Drug: rosiglitazone; 4 mg daily for 6 months; Other Names: Avandia
Active Comparator: Drospirenone/ethinyl estradiol; Treatment naive overweight adolescent females with PCOS treated with Drospirenone/ethinyl estradiol	Drug: drospirenone/ethinyl estradiol; 1 tab (3mg/30mcg) daily for 6 months; Other Names: Yasmin
No Intervention: Overweight/Obese without PCOS; Overweight adolescent females without PCOS to use as comparison of normal developmental changes. *No participants were enrolled in this Arm.
No Intervention: Lean without PCOS; Lean healthy girls without PCOS to serve as controls for the cardiovascular markers. *No participants were enrolled in this Arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral Insulin Sensitivity at Baseline and 6 Months.	Peripheral insulin sensitivity was evaluated during the hyperinsulinemic-euglycemic clamp.	Baseline and 6 months
Hepatic Insulin Sensitivity at Baseline and 6 Months.	Hepatic insulin sensitivity was evaluated prior to the hyperinsulinemic-euglycemic clamp.	Baseline and 6 months
Glucose Tolerance Status at Baseline and 6 Months.	Glucose tolerance status was classified according to the ADA (American Diabetes Association) criteria.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Fat Mass at Baseline and 6 Months	DXA (dual-energy x-ray absorptiometry) scans were done to measure total fat mass.	Baseline and 6 months
Total Testosterone at Baseline and 6 Months	Total testosterone was measured by HPLC(high-performance liquid chromatography)-tandem mass spectroscopy.	Baseline and 6 months
Percent Body Fat at Baseline and 6 Months	DXA scans were done to measure the percentage of body fat.	Baseline and 6 months
Free Testosterone at Baseline and 6 Months	Free testosterone was measured by equilibrium dialysis.	Baseline and 6 months
SHBG at Baseline and 6 Months	SHBG (sex hormone-binding globulin) was measured by immunoradiometric assay.	Baseline and 6 months
DHEAS at Baseline and 6 Months	DHEAS (dehydroepiandrosterone sulfate) was measured by radioimmunoassay in dilute serum after hydrolysis.	Baseline and 6 months
Delta Androstenedione at Baseline and 6 Months	Delta Androstenedione was measured by HPLC-tandem mass spectroscopy.	Baseline and 6 months
Delta DHEA at Baseline and 6 Months	Delta DHEA was measured by HPLC-tandem mass spectroscopy.	Baseline and 6 months
Delta 17-OHProg at Baseline and 6 Months	Delta 17-OHProg (17-hydroxyprogesterone) was measured by HPLC-tandem mass spectroscopy.	Baseline and 6 months
Delta 17-OHPreg at Baseline and 6 Months	Delta 17-OHPreg (17-hydroxypregnenolone) was measured by HPLC-tandem mass spectroscopy.	Baseline and 6 months
Cholesterol at Baseline and 6 Months	Cholesterol was measured using the standards of the Centers for Disease Control and Prevention.	Baseline and 6 months
HDL at Baseline and 6 Months	HDL (high-density lipoprotein) was measured using the standards of the Centers for Disease Control and Prevention.	Baseline and 6 months
LDL at Baseline and 6 Months	LDL (low-density lipoprotein) was measured using the standards of the Centers for Disease Control and Prevention.	Baseline and 6 months
Triglycerides at Baseline and 6 Months	Triglycerides were measured using the standards of the Centers for Disease Control and Prevention.	Baseline and 6 months
Non-HDL Cholesterol at Baseline and 6 Months	Non-HDL cholesterol was measured using the standards of the Centers for Disease Control and Prevention.	Baseline and 6 months
Adiponectin at Baseline and 6 Months	Adiponectin was measured by radioimmunoassay.	Baseline and 6 months
Leptin at Baseline and 6 Months	Leptin was measured by radioimmunoassay.	Baseline and 6 months
Hs-CRP at Baseline and 6 Months	hs-CRP(high-sensitivity C-reactive protein) was measured by COAG-Nephelometry.	Baseline and 6 months
Morning Blood Pressure at Baseline and 6 Months	Morning blood pressure was measured with an automated sphygmomanometer.	Baseline and 6 months
Night Blood Pressure at Baseline and 6 Months	Night blood pressure was measured with an automated sphygmomanometer.	Baseline and 6 months

Collaborators and Investigators

• Sponsor: Silva Arslanian
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Silva Arslanian, M.D., University of Pittsburgh

Publications and helpful links

General Publications

• Tfayli H, Ulnach JW, Lee S, Sutton-Tyrrell K, Arslanian S. Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors. J Clin Endocrinol Metab. 2011 May;96(5):1311-9. doi: 10.1210/jc.2010-2547. Epub 2011 Feb 16.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: March 18, 2008
• First Submitted That Met QC Criteria: March 18, 2008
• First Posted (Estimate): March 21, 2008

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: October 16, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Hyperinsulinism; Polycystic Ovary Syndrome; Syndrome; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Natriuretic Agents; Diuretics; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Estradiol; Ethinyl Estradiol; Rosiglitazone; Drospirenone; Drospirenone and ethinyl estradiol combination
• Other Study ID Numbers: 0503013; 2K24HD001357 (U.S. NIH Grant/Contract)