NCT00704912

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
217

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2008

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 23, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 25, 2008

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2008

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

December 17, 2015

Completed
Last Updated

November 7, 2016

Status Verified

November 1, 2016

Enrollment Period

5.5 years

First QC Date

June 23, 2008

Results QC Date

November 13, 2015

Last Update Submit

November 3, 2016

Conditions

Polycystic Ovary Syndrome

Keywords

Polycystic Ovary Syndrome

Outcome Measures

Primary Outcomes (1)

  • 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.

Secondary Outcomes (3)

  • Ovulation Rate

    Up to 4 months

  • Change in Weight

    Baseline, 4 months

  • Prevalence of Metabolic Syndrome

    Baseline, 4 months

Study Arms (3)

Lifestyle intervention

ACTIVE COMPARATOR

Orlistat/Meal Replacement/Lifestyle Modification

Drug: Orlistat/Meal Replacement/Lifestyle Modification

Oral Contraceptives (OCP)

ACTIVE COMPARATOR

Loestrin 1/20

Drug: Loestrin 1/20

Lifestyle/OCP Combined

ACTIVE COMPARATOR

Combination of treatments

Drug: Combination of treatments

Interventions

Orlistat/Meal Replacement/Lifestyle ModificationDRUG

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.

Also known as: Orlistat, Alli, Lifestyle Intervention, Weight Loss
Lifestyle intervention
Loestrin 1/20DRUG

Patients will be started on a low dose containing OCP for a continuous 4 month period.

Also known as: OCP, Oral Contraceptive
Oral Contraceptives (OCP)
Combination of treatmentsDRUG

Medications will be administered as described for the other 2 arms.

Also known as: Orlistat, Alli, OCP, Oral Contraceptive, Weight Loss, Lifestyle Intervention
Lifestyle/OCP Combined

Eligibility Criteria

Age18 Years - 40 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • 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.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania, Department of Obstetrics and Gynecology

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (5)

  • Steinberg Weiss M, Roe AH, Allison KC, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, Gnatuk CL, Estes SJ, Sarwer DB, Coutifaris C, Legro RS, Dokras A. Lifestyle modifications alone or combined with hormonal contraceptives improve sexual dysfunction in women with polycystic ovary syndrome. Fertil Steril. 2021 Feb;115(2):474-482. doi: 10.1016/j.fertnstert.2020.08.1396. Epub 2020 Oct 12.

    PMID: 33059886DERIVED

  • Shah A, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Gnatuk CL, Estes SJ, Allison KC, Sarwer DB, Sluss PM, Coutifaris C, Dokras A, Legro RS. Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ss Superfamily Hormones in PCOS. J Clin Endocrinol Metab. 2021 Jan 1;106(1):108-119. doi: 10.1210/clinem/dgaa682.

    PMID: 32968804DERIVED

  • Dokras A, Sarwer DB, Allison KC, Milman L, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, Gnatuk CL, Estes SJ, Fleming J, Coutifaris C, Legro RS. Weight Loss and Lowering Androgens Predict Improvements in Health-Related Quality of Life in Women With PCOS. J Clin Endocrinol Metab. 2016 Aug;101(8):2966-74. doi: 10.1210/jc.2016-1896. Epub 2016 Jun 2.

    PMID: 27253669DERIVED

  • Legro RS, Dodson WC, Kunselman AR, Stetter CM, Kris-Etherton PM, Williams NI, Gnatuk CL, Estes SJ, Allison KC, Sarwer DB, Diamond MP, Schlaff WD, Casson PR, Christman GM, Barnhart KT, Bates GW, Usadi R, Lucidi S, Baker V, Zhang H, Eisenberg E, Coutifaris C, Dokras A. Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS. J Clin Endocrinol Metab. 2016 Jul;101(7):2658-66. doi: 10.1210/jc.2016-1659. Epub 2016 May 12.

    PMID: 27172435DERIVED

  • Legro RS, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, Gnatuk CL, Estes SJ, Fleming J, Allison KC, Sarwer DB, Coutifaris C, Dokras A. Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2015 Nov;100(11):4048-58. doi: 10.1210/jc.2015-2778. Epub 2015 Sep 24.

    PMID: 26401593DERIVED

Related Links

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

OrlistatContraceptives, Oral

Condition Hierarchy (Ancestors)

Ovarian CystsCystsNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGonadal DisordersEndocrine System Diseases

Intervention Hierarchy (Ancestors)

LactonesOrganic ChemicalsContraceptive Agents, FemaleContraceptive AgentsReproductive Control AgentsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesTherapeutic Uses

Results Point of Contact

Title
Richard S. Legro, M.D.
Organization
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
rsl1@psu.edu
717-531-8478

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Obstetrics and Gynecology and Public Health Sciences

Study Record Dates

First Submitted

June 23, 2008

First Posted

June 25, 2008

Study Start

September 1, 2008

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

November 7, 2016

Results First Posted

December 17, 2015

Record last verified: 2016-11

Locations

US(2)