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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01070160
First received: February 16, 2010
Last updated: June 13, 2014
Last verified: June 2014

February 16, 2010
June 13, 2014
June 2009
July 2013   (final data collection date for primary outcome measure)
  • 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 ]
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, 3 month, and 9 month marks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01070160 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Endometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)
Endometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

blood, endometrium tissue biopsy

Probability Sample

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.

Polycystic Ovarian Syndrome
  • Drug: Endometrin (progesterone 100mg vaginal inserts)
    once a day, 6-8 days as specified (prior to each EMBx)
  • Drug: Metformin
    per clinical care guidelines
  • A
    Women with PCOS initiating Metformin and exposure to vaginal progesterone for 6-8 days prior ro Endometrium Biopsy
    Interventions:
    • Drug: Endometrin (progesterone 100mg vaginal inserts)
    • Drug: Metformin
  • B
    Women with PCOS not planning initiating Metformin and exposure to vaginal progesterone for 6-8 days prior to Endometrium Biopsy
    Intervention: Drug: Endometrin (progesterone 100mg vaginal inserts)
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
July 2013
July 2013   (final data collection date for primary outcome measure)

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
Female
18 Years to 42 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01070160
U54 HD 052668-02, U54HD052668-02
No
Yale University
Yale University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Lubna Pal, MBBS MRCOG MSc Yale University
Yale University
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP