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

November 3, 2016 updated by: Richard S. Legro, M.D., Milton S. Hershey Medical Center

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. The investigators 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 is to improve insulin sensitivity with weight loss.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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. Orlistat is a gastric lipase inhibitor that reduces the absorption of fat contained in a meal by about 30%. 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.

Study Type

Interventional

Enrollment (Actual)

217

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania, Department of Obstetrics and Gynecology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 38 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Couples Inclusion Criteria:

  • Partner with sperm concentration of >=14 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 one patent tube and normal uterine cavity as determined by sonohysterogram, hysterosalpingogram, or hysteroscopy/laparoscopy within the last 3 years, or confirmation of a intrauterine pregnancy within the past 2 years.
  • No previous sterilization procedures(vasectomy, tubal ligation) that have been reversed.
  • Wanting to seek pregnancy.

Inclusion Criteria:

  • Chronic anovulation or oligomenorrhea defined as intermenstrual periods of >= 45 days or a total of <=8 periods per year.
  • Hyperandrogenism will be an elevated total testosterone >=50 ng/dL.
  • Hirsutism determined by a modified Ferriman-Gallwey Score >8.
  • PCO on ultrasound (12 or more follicles measuring 2-9 mm in diameter).
  • BMI >=27 to <=42.
  • Normal EKG to rule out any abnormalities with the heart.

Exclusion Criteria:

  • Current pregnancy.
  • Patients on oral contraceptives, depo progestins, or hormonal implants.
  • Patients with hyperprolactinemia defined as two prolactin levels at least one week apart >30 ng/mL.
  • Patients with known 21-hydroxylase deficiency by a fasting 17-hydroxyprogesterone (17-OHP) level <2 ng/mL and ACTH stimulation test as needed, or other enzyme deficiency.
  • Patients with menopausal FSH levels >20 mIU/mL.
  • Patients with uncorrected thyroid disease (TSH <0.45 mIU/ML or >4.5 mIU/ML).
  • Patients diagnosed with Type1 or Type II diabetes.
  • Patients with liver disease defined as AST or ALT >2 times normal or total bilirubin >2.5 mg/dL.
  • Patients with renal disease defined as BUN >30 mg/dL or serum creatinine >1.4 mg/dL.
  • Patients with significant anemia (Hemoglobin <10 mg/dL).
  • Patients with a history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.
  • Patients with known heart disease that is likely to be exacerbated by pregnancy.
  • Patients with a history of , or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma. A normal PAP smear or reassuring colposcopy based on current ACOG guidelines will be required.
  • Patient with current history of alcohol abuse.
  • Patients enrolled simultaneously into other investigative studies.
  • Patients taking other medications know to affect reproductive function or metabolism.
  • Patients with a suspected adrenal or ovarian tumor secreting androgens.
  • Patients with suspected Cushing's syndrome.
  • Patients who have undergone a bariatric surgery procedure in the recent past (<12 months).
  • Patients with untreated poorly controlled hypertension defined as systolic blood pressure >=150 mm Hg or average diastolic >=100 mm Hg on three measurements obtained 5 minutes apart. If treated, average systolic blood pressure >= 140 mm Hg or average diastolic >= 90 mm Hg.
  • Patients with medical conditions that represent contraindications to orlistat, OCP, clomiphene, and/or pregnancy.
  • Patients currently participating in lifestyle intervention program (Weight Watchers, Atkins Diet, Curves) or lost more than 5% body weight within the last 6 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lifestyle intervention
Orlistat/Meal Replacement/Lifestyle Modification
Drug: Orlistat/Meal Replacement/Lifestyle Modification
Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
Other Names:
  • Alli
  • Weight Loss
  • Orlistat
  • Lifestyle Intervention
Active Comparator: Oral Contraceptives (OCP)
Loestrin 1/20
Drug: Loestrin 1/20
Patients will be started on a low dose containing OCP for a continuous 4 month period.
Other Names:
  • OCP
  • Oral Contraceptive
Active Comparator: Lifestyle/OCP Combined
Combination of treatments
Drug: Combination of treatments
Medications will be administered as described for the other 2 arms.
Other Names:
  • Alli
  • Weight Loss
  • OCP
  • Orlistat
  • Lifestyle Intervention
  • Oral Contraceptive

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Live Birth Rate
Time Frame: Participants were followed for 4 months of attempted conception and those who conceived were then followed for the duration of their pregnancy, approximately 9 months.
Participants were followed for 4 months of attempted conception and those who conceived were then followed for the duration of their pregnancy, approximately 9 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ovulation Rate
Time Frame: Up to 4 months
Up to 4 months
Change in Weight
Time Frame: Baseline, 4 months
Change from baseline to end of the 4-month intervention.
Baseline, 4 months
Prevalence of Metabolic Syndrome
Time Frame: Baseline, 4 months
Baseline, 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Milton S. Hershey Medical Center

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

June 23, 2008

First Submitted That Met QC Criteria

June 23, 2008

First Posted (Estimate)

June 25, 2008

Study Record Updates

Last Update Posted (Estimate)

November 6, 2016

Last Update Submitted That Met QC Criteria

November 3, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27184

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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