Official Title: “Treatment of Hyperandrogenism vs. Insulin Resistance in Infertile PCOS Women”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study

Study Primary Completion Date: March 2013

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.

Intervention(s) in this Clinical Trial

• 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.
• Drug: Loestrin 1/20
  • Patients will be started on a low dose containing OCP for a continuous 4 month period.
• Drug: Sibutramine (Meridia) and Loestrin 1/20
  • Medications will be administered as described for Arm A and Arm B.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Phase 1, Arm A
  • Weight Loss via Medication/Meal Replacement/Lifestyle Modification
• Active Comparator: Phase 1, Arm B
  • Reducing HA will consist of continuous low dose OCP
• Active Comparator: Phase 1, Arm C
  • Combination of treatments from Arm A and Arm B

Primary 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
    Safety Issue?: Yes

Secondary 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
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Penn State University

Overall Clinical Trial Officials and Contacts

Richard S Legro, M.D. Principal Investigator Penn State College of Medicine, Penn State Milton S. Hershey Medical Center  

Overall Contact: Patricia D Rawa, BS 717-531-3692 prawa@hmc.psu.edu

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00704912

Study ID Number: 27184

ClinicalTrials.gov Identifier: NCT00704912

Health Authority: United States: Institutional Review Board

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