Insulin Resistance, Polycystic Ovary Syndrome, and Bone Research Study

• ClinicalTrials.gov Identifier: NCT00640224
• Recruitment Status: Completed
• First Posted: March 21, 2008
• Results First Posted: November 17, 2017
• Last Update Posted: November 17, 2017
• Sponsor: Silva Arslanian
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Silva Arslanian, University of Pittsburgh

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Polycystic Ovary Syndrome	Drug: rosiglitazone; Drug: drospirenone/ethinyl estradiol	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Obesity, Insulin Resistance, and Bone Metabolism in Adolescents With PCOS: Effects of Insulin Sensitizers Versus Oral Contraceptives
• Study Start Date: March 2005
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: July 2015

Arms and Interventions

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 Name: 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 Name: 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, Pennsylvania

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15224

Sponsors and Collaborators

Silva Arslanian

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Silva Arslanian, M.D.; University of Pittsburgh

More Information

Publications of Results:

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.

• Responsible Party: Silva Arslanian, Principal Investigator, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00640224
• Other Study ID Numbers: 0503013; 2K24HD001357 ( U.S. NIH Grant/Contract )
• First Posted: March 21, 2008
• Results First Posted: November 17, 2017
• Last Update Posted: November 17, 2017
• Last Verified: October 2017

Additional relevant MeSH terms:

Polycystic Ovary Syndrome; Insulin Resistance; Syndrome; Disease; Pathologic Processes; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Rosiglitazone; Drospirenone; Ethinyl Estradiol; Drospirenone and ethinyl estradiol combination; Estradiol; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal