Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (PCOS) Women - Full Text View

Sponsors and Collaborators:	Penn State University University of Pennsylvania
Information provided by:	Penn State University
ClinicalTrials.gov Identifier:	NCT00704912

Purpose

The goal of this three-armed randomized controlled trial is to establish the relative roles of treatment of hyperandrogenism versus obesity (as the largest modifiable factor contributing to insulin resistance) in treating infertility and improving pregnancy outcomes among obese PCOS women. We hypothesize that the key to restoring ovulation leading to live birth is to correct hyperandrogenism with oral contraceptive pills, but the key to avoiding later pregnancy complications isto improve insulin sensitivity with weight loss.

Condition	Intervention	Phase
Polycystic Ovary Syndrome	Drug: Sibutramine (Meridia) and Lifestyle Intervention with exercise and diet Drug: Loestrin 1/20 Drug: Sibutramine (Meridia) and Loestrin 1/20	Phase I

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	Treatment of Hyperandrogenism vs. Insulin Resistance in Infertile PCOS Women

Resource links provided by NLM:

MedlinePlus related topics: Diets Infertility Obesity Weight Control

Drug Information available for: Insulin Modicon Sibutramine Sibutramine hydrochloride monohydrate Ethinyl estradiol mixture with norethindrone Norinyl

U.S. FDA Resources

Further study details as provided by Penn State University:

Primary Outcome Measures:

Identify the effects of weight loss vs. OCP therapy on the PCOS reproductive phenotype. Pretreatment with OCP will most improve the preconception PCOS phenotype compared to weight loss, and the combination of both will be the best. [ Time Frame: Assessed during data analysis ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Compare impact of weight loss vs. OCP vs. the combination of both on the live birth rate. The live birth rate will be lowest in the weight loss group, higher in the OCP group and highest in the group treated with both. [ Time Frame: At time of data analysis ] [ Designated as safety issue: No ]

Estimated Enrollment:	246
Study Start Date:	September 2008
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Phase 1, Arm A: Active Comparator Weight Loss via Medication/Meal Replacement/Lifestyle Modification	Drug: Sibutramine (Meridia) and Lifestyle Intervention with exercise and diet Sibutramine will be initiated at a dose of 5 mg/day. The dose will be increased over the following visits from 5 mg/day to a maximum of 15 mg/day.
Phase 1, Arm B: Active Comparator Reducing HA will consist of continuous low dose OCP	Drug: Loestrin 1/20 Patients will be started on a low dose containing OCP for a continuous 4 month period.
Phase 1, Arm C: Active Comparator Combination of treatments from Arm A and Arm B	Drug: Sibutramine (Meridia) and Loestrin 1/20 Medications will be administered as described for Arm A and Arm B.

Detailed Description:

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility among women, and women with PCOS are at increased risk for pregnancy complications such as gestational diabetes and pre-eclampsia. Both hyperandrogenism (HA) and obesity exacerbated insulin resistance (IR) are characteristics of the syndrome, and are targets for treatment, but which should be the predominant focus is still unknown. Phase 1 of this study will be a randomized trial of three preconception interventions in infertile women with PCOS. The first arm will be a combined intervention of medication, meal replacements, and lifestyle modification to improve IR. Sibutramine is a combined norepinephrine-serotonin re-uptake inhibitor that is associated with increased satiation (fullness) and a resulting reduction in food intake. The second arm will be the use of a continuous OCP for 4 months to improve HA. Lo-Estrin 1/20 will be used in a continuous method for 4 months to suppress the ovary. The third arm is the combination of both to improve HA an IR. Phase II of this study will involve ovulation induction with clomiphene citrate with hopeful outcome of pregnancy. Finally, Phase III involve following the pregnancies for outcomes and complications.

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Partner with sperm concentration of >=20 million/mL in at least one ejaculate with motile sperm.
Ability to have regular intercourse 2-3 times per week during the ovulation induction phase of study.
At least on patent tube and normal uterine cavity as determined by sonohysterogram, hysterosalpingogram, or hysteroscopy/laparoscopy within the last 3 years.
No previous sterilization procedures(vasectomy, tubal ligation) tha have been reversed.

Exclusion Criteria:

Intermenstrual periods of >= 45 days or a total of <=8 periods per year.
Elevated total testosterone >50 ng/dL.
PCO on ultrasound (12 or more follicles measuring 2-9 mm in diameter).
BMI >=27 to <=40.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704912

Contacts

Contact: Patricia D Rawa, BS	717-531-3692	prawa@hmc.psu.edu
Contact: Karen Lecks	215-349-5201	klecks@obgyn.upenn.edu

Locations

United States, Pennsylvania
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center	Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Richard S. Legro, M.D. 717-531-8478 rsl1@psu.edu
Contact: Patsy Rawa, B.S. 717-531-3692 prawa@psu.edu
Principal Investigator: Richard S Legro, M.D.
University of Pennsylvania, Department of Obstetrics and Gynecology	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Christos Coutifaris, M.D., Ph.D. 215-662-6100 ccoutifaris@obgyn.upenn.edu
Contact: Karen Lecks 215-349-5201 klecks@obgyn.upenn.edu
Principal Investigator: Christos Coutifaris, M.D., Ph.D.

Sponsors and Collaborators

Penn State University

University of Pennsylvania

Investigators

Principal Investigator:	Richard S Legro, M.D.	Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
Principal Investigator:	Christos Coutifaris, M.D., Ph.D.	Universtiy of Pennsylvania, Department of Obstetrics and Gynecology

More Information

Additional Information:

Click here for more information about this study. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Penn State College of Medicine, Penn State Milton S. Hershey Medical Center ( Dr. Richard S. Legro, M.D. )
Study ID Numbers:	27184, 1 RO1 HD056510-01 A1
Study First Received:	June 23, 2008
Last Updated:	January 29, 2009
ClinicalTrials.gov Identifier:	NCT00704912 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Penn State University:

Polycystic Ovary Syndrome

Study placed in the following topic categories:

Infertility
Modicon
Gonadal Disorders
Contraceptive Agents
Contraceptives, Oral
Psychotropic Drugs
Contraceptive Agents, Female
Hyperandrogenism
Ovarian Diseases
Sex Differentiation Disorders
Polycystic Ovarian Syndrome
Insulin
Genital Diseases, Female
Sibutramine
Contraceptives, Oral, Sequential

Hyperinsulinism
Appetite Depressants
Metabolic Disorder
Antidepressive Agents
Metabolic Diseases
Endocrine System Diseases
Cysts
Norinyl
Contraceptives, Oral, Combined
Anti-Obesity Agents
Contraceptives, Oral, Hormonal
Polycystic Ovary Syndrome
Insulin Resistance
Endocrinopathy
Glucose Metabolism Disorders

Additional relevant MeSH terms:

Modicon
Gonadal Disorders
Contraceptive Agents
Contraceptives, Oral
Physiological Effects of Drugs
Psychotropic Drugs
Contraceptive Agents, Female
Hyperandrogenism
Ovarian Diseases
Reproductive Control Agents
Sex Differentiation Disorders
Genital Diseases, Female
Sibutramine
Contraceptives, Oral, Sequential
Hyperinsulinism

Pathologic Processes
Therapeutic Uses
Syndrome
Appetite Depressants
Contraceptives, Oral, Synthetic
Antidepressive Agents
Metabolic Diseases
Disease
Endocrine System Diseases
Cysts
Norinyl
Pharmacologic Actions
Adnexal Diseases
Contraceptives, Oral, Combined
Anti-Obesity Agents

ClinicalTrials.gov processed this record on July 02, 2009