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

This study has been completed.
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
Richard S. Legro, M.D., Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT00704912
First received: June 23, 2008
Last updated: October 7, 2014
Last verified: October 2014
  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. 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.


Condition Intervention Phase
Polycystic Ovary Syndrome
Drug: Orlistat/Meal Replacement/Lifestyle Modification
Drug: Loestrin 1/20
Drug: Combination of treatments
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Hyperandrogenism vs. Insulin Resistance in Infertile PCOS Women

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • Trends in live birth [ Time Frame: When the study and data analysis is completed in 5 Years ] [ Designated as safety issue: No ]
    The investigators will wait until study is completed to review change in Body Mass Index, Free Androgen Index and Proinsulin on these subjects when study is completed


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: When the study and data analysis is completed in 5 Years ] [ Designated as safety issue: No ]

Enrollment: 217
Study Start Date: September 2008
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Orlistat, Alli, Lifestyle Intervention, Polycystic Ovary Syndrome, PCOS, Weight Loss, Pregnancy
Active Comparator: 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 Name: Orlistat, Alli, Weight Loss, OCP, Oral Contraceptive, PCOS, Polycystic Ovary Syndrome, Pregnancy
Active Comparator: Lifestyle/OCP Combined
Combination of treatments
Drug: Combination of treatments
Medications will be administered as described for the other 2 arms.
Other Name: Orlistat, Alli, OCP, Oral Contraceptive, Weight Loss, Lifestyle Intervention, Pregnancy, Polycystic Ovary Syndrome, PCOS

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Pennsylvania
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania, Department of Obstetrics and Gynecology
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Milton S. Hershey Medical Center
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:
No publications provided

Responsible Party: Richard S. Legro, M.D., Professor, Obstetrics and Gynecology and Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00704912     History of Changes
Other Study ID Numbers: 27184, 1 RO1 HD056510-01 A1
Study First Received: June 23, 2008
Last Updated: October 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Milton S. Hershey Medical Center:
Polycystic Ovary Syndrome

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Hyperandrogenism
Insulin Resistance
Syndrome
46, XX Disorders of Sex Development
Adnexal Diseases
Adrenogenital Syndrome
Congenital Abnormalities
Cysts
Disease
Disorders of Sex Development
Endocrine System Diseases
Genital Diseases, Female
Glucose Metabolism Disorders
Gonadal Disorders
Hyperinsulinism
Metabolic Diseases
Neoplasms
Ovarian Cysts
Ovarian Diseases
Pathologic Processes
Urogenital Abnormalities
Contraceptive Agents
Contraceptives, Oral
Orlistat
Anti-Obesity Agents
Central Nervous System Agents
Contraceptive Agents, Female
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 27, 2014