Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (PCOS) Women (OWL-PCOS)
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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 (Alli) and Lifestyle Intervention with exercise and diet Drug: Loestrin 1/20 Drug: Orlistat (Alli) and Loestrin 1/20 |
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 |
- Identify the effects of weight loss vs. OCP therapy on the PCOS reproductive phenotype [ 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
- 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 ]
| 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 |
|---|---|
|
Active Comparator: Phase 2, Arm A
Weight Loss via Medication/Meal Replacement/Lifestyle Modification
|
Drug: Orlistat (Alli) and Lifestyle Intervention with exercise and diet
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: Phase 2, Arm B
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.
Other Name: Orlistat, Alli, Weight Loss, OCP, Oral Contraceptive, PCOS, Polycystic Ovary Syndrome, Pregnancy
|
|
Active Comparator: Phase 2, Arm C
Combination of treatments from Arm A and Arm B
|
Drug: Orlistat (Alli) and Loestrin 1/20
Medications will be administered as described for Arm A and Arm B.
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 |
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 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| 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 | |
| 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: | December 28, 2012 |
| 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 Insulin Resistance Hyperandrogenism Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases Ovarian Cysts Cysts Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Gonadal Disorders Endocrine System Diseases 46, XX Disorders of Sex Development |
Disorders of Sex Development Urogenital Abnormalities Adrenogenital Syndrome Congenital Abnormalities Contraceptive Agents Norinyl Ethynylestradiol mixture with norethindrone Contraceptives, Oral Orlistat Reproductive Control Agents Physiological Effects of Drugs Pharmacologic Actions Therapeutic Uses Contraceptive Agents, Female Contraceptives, Oral, Combined |
ClinicalTrials.gov processed this record on May 19, 2013