Endometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)

This study is currently recruiting participants.
Verified February 2013 by Yale University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01070160
First received: February 16, 2010
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

The investigators aim is to conduct a prospective un-blinded pilot study of premenopausal women diagnosed with Polycystic Ovarian Syndrome (PCOS), defined using criteria developed at the 1990 NICHD conference on PCOS, undergoing treatment for ovulation induction with Metformin. We propose that improving insulin sensitivity with use of Metformin in women diagnosed with PCOS has facilitatory influences on the uterine endometrium.


Condition Intervention
Polycystic Ovarian Syndrome
Drug: Endometrin (progesterone 100mg vaginal inserts)
Drug: Metformin

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Endometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • It is anticipated that endometrial expression of implantation markers will be upregulated by metformin treatment compared to baseline and improved parameters will be identified with longer duration of metformin exposure. endometrium biopsy [ Time Frame: baseline ] [ Designated as safety issue: Yes ]
  • It is anticipated that endometrial expression of implantation markers will be upregulated by metformin treatment compared to baseline and improved parameters will be identified with longer duration of metformin exposure. endometrium biopsy [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • It is anticipated that endometrial expression of implantation markers will be upregulated by metformin treatment compared to baseline and improved parameters will be identified with longer duration of metformin exposure. endometrium biopsy [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • blood draw (20mL) [ Time Frame: on day of EMBx ] [ Designated as safety issue: Yes ]
  • A combination of quantitative real time PCR, immunohistochemistry, and Western Blot techniques will be utilized for studying endometrial markers of receptivity in the endometrial tissue [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood, endometrium tissue biopsy


Estimated Enrollment: 30
Study Start Date: June 2009
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
A
Women with PCOS initiating Metformin and exposure to vaginal progesterone for 6-8 days prior ro Endometrium Biopsy
Drug: Endometrin (progesterone 100mg vaginal inserts)
once a day, 6-8 days as specified (prior to each EMBx)
Drug: Metformin
per clinical care guidelines
B
Women with PCOS not planning initiating Metformin and exposure to vaginal progesterone for 6-8 days prior to Endometrium Biopsy
Drug: Endometrin (progesterone 100mg vaginal inserts)
once a day, 6-8 days as specified (prior to each EMBx)
Women with PCOS who previously initiated metformin
Women with PCOS who initiated metformin at least 3 months prior to enrollment who have completed a 6-10 day course of progesterone

Detailed Description:

Endometrial assessments are proposed following three month and then nine month treatment with metformin; expression of specified markers at respective time points will be compared to baseline.

Visit 1: Screening

  • Signed informed consent
  • Comprehensive history intake
  • Physical exam: Vital signs, height, weight, waist circumferences, waist : hip ratio
  • Urine pregnancy test
  • Subjects provided with a 10 day supply of vaginal progesterone and EMBx will be scheduled between days 6-8 of progesterone use.

Visit 2: Baseline

  • Urine pregnancy test
  • Endometrium thickness will be measured via transvaginal ultrasound
  • EMBx: sample of endometrial tissue will be sent for histopathology to rule out endometrial hyperplasia or cancer
  • 20cc blood
  • Metformin prescription and dispensing will be as per clinical care.
  • Women will be advised to use barrier method of contraception (ie; condoms, contraceptive jellies or foam, sponge, diaphragm, or cervical cap) for the duration of the study.

Visits 3 and 5 (Weeks 8-10 and 30-34, respectively)

  • Urine pregnancy test
  • A 10 day course of vaginal progesterone to allow scheduling of EMBx's time points specified under visit 1

Visits 4 and 6 (Weeks 12 ± 1 week and 36 ± 1 week respectively)

- The procedure specified for baseline (Visit 2) will be repeated.

  Eligibility

Ages Eligible for Study:   18 Years to 42 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Women will be recruited from the multi-physician Yale Reproductive Endocrinology clinical practice and Yale Fertility Center. Metformin is a routinely employed therapeutic strategy utilized for managing PCOS by practitioners at YFC. Almost 1/3 of the patients with PCOS are not interested in pursuing fertility in the immediate future and it is these patients who will be offered participation in the trial.

Criteria

Inclusion Criteria:

  • Premenopausal between 18-42 years of age
  • Diagnosed with PCOS as defined by chronic oligo- or amenorrhea (8 menstrual periods annually); biochemical hyperandrogenemia (elevated total or free testosterone) and /or clinical hyperandrogenism (excessive facial hair &/or acne); exclusion of common medical disorders (normal thyroid function tests and serum prolactin and exclusion of 21-hydroxylase deficiency by a fasting 17-hydroxyprogesterone <200 ng/dl).
  • Acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (CBC, SMA20, urinalysis) performed within the past 6 months
  • Able to provide signed informed consent
  • Able to comply with study requirements
  • Willing to delay the start of clinically prescribed metformin treatment

Exclusion Criteria:

  • Known diabetics or those with clinically significant and known pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer)
  • Current use of hormonal contraceptives
  • Seeking pregnancy; use of fertility drugs within 6 months of study
  • Current or recent (within 3 months) use of metformin
  • Ingestion of any investigational drug within two months prior to study onset
  • Evidence of endometrial hyperplasia or cancer upon baseline EMBx
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01070160

Contacts
Contact: Lubna Pal, MBBS MRCOG MSc (203)-737-5619 lubna.pal@yale.edu
Contact: Joanne Williams, BSN (203)-785-3463 joanne.williams@yale.edu

Locations
United States, Connecticut
Yale-New Haven Hospital Women's Center Recruiting
New Haven, Connecticut, United States, 06520-8063
Contact: Lubna Pal, MBBS MRCOG MSc    (203)-737-5619    lubna.pal@yale.edu   
Sub-Investigator: Hugh Taylor, MD         
Sub-Investigator: Beth Rackow, MD         
Sub-Investigator: Pinar Kodaman, MD/PhD         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Lubna Pal, MBBS MRCOG MSc Yale University
  More Information

Additional Information:
No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01070160     History of Changes
Other Study ID Numbers: U54 HD 052668-02, U54HD052668-02
Study First Received: February 16, 2010
Last Updated: February 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Polycystic Ovarian Syndrome (PCOS)
Metformin
Endometrin

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Metformin
Progesterone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 22, 2014