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

Polycystic Ovary Syndrome Clinical Trial

— OWL-PCOS  

Official title:

Treatment of Hyperandrogenism vs. Insulin Resistance in Infertile PCOS Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00704912
• Other study ID #: 27184
• Status: Completed
• Phase: Phase 2
• First received: June 23, 2008
• Last updated: November 3, 2016
• Start date: September 2008
• Est. completion date: March 2014

Study information

• Verified date: November 2016
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperandrogenism
• Insulin Resistance
• Polycystic Ovary Syndrome
• Syndrome

Intervention

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.
• Loestrin 1/20
Patients will be started on a low dose containing OCP for a continuous 4 month period.
• Combination of treatments
Medications will be administered as described for the other 2 arms.

Locations

Country	Name	City	State
United States	Penn State College of Medicine, Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Pennsylvania, Department of Obstetrics and Gynecology	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live Birth Rate		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.	No
Secondary	Ovulation Rate		Up to 4 months	No
Secondary	Change in Weight	Change from baseline to end of the 4-month intervention.	Baseline, 4 months	No
Secondary	Prevalence of Metabolic Syndrome		Baseline, 4 months	No

External Links

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