Treatment of Hyperandrogenism vs. Insulin Resistance in Infertile PCOS Women - Full Text View

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

MedlinePlus related topics:

Infertility Obesity Weight Control

ChemIDplus related topics:

Insulin Sibutramine Sibutramine hydrochloride monohydrate Modicon Norinyl

U.S. FDA Resources

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

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

Locations


United States, Pennsylvania
	Penn State College of Medicine, Penn State Milton S. Hershey Medical Center	Not yet recruiting
	Hershey, Pennsylvania, United States, 17033
	Contact: Richard S. Legro, M.D. 717-531-8478 rsl1@psu.edu
	Principal Investigator: Richard S Legro, M.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

More Information

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

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
First Received:	June 23, 2008
Last Updated:	June 23, 2008
ClinicalTrials.gov Identifier:	NCT00704912
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

Metabolic Diseases

Gonadal Disorders

Endocrine System Diseases

Hyperandrogenism

Ovarian Diseases

Cysts

Norinyl

Insulin

Sibutramine

Genital Diseases, Female

Hyperinsulinism

Polycystic Ovary Syndrome

Endocrinopathy

Insulin Resistance

Metabolic disorder

Glucose Metabolism Disorders

Ovarian Cysts

Additional relevant MeSH terms:

Disease

Contraceptive Agents

Contraceptives, Oral

Physiological Effects of Drugs

Psychotropic Drugs

Contraceptive Agents, Female

Reproductive Control Agents

Sex Differentiation Disorders

Pharmacologic Actions

Adnexal Diseases

Contraceptives, Oral, Combined

Anti-Obesity Agents

Contraceptives, Oral, Sequential

Neoplasms

Pathologic Processes

Contraceptives, Oral, Hormonal

Therapeutic Uses

Syndrome

Appetite Depressants

Contraceptives, Oral, Synthetic

Central Nervous System Agents

Antidepressive Agents

ClinicalTrials.gov processed this record on September 23, 2008

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