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

Overview[ - collapse ][ - ]

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.
ConditionPolycystic Ovarian Syndrome
InterventionDrug: Endometrin (progesterone 100mg vaginal inserts)
Drug: Metformin
PhaseN/A
SponsorYale University
Responsible PartyYale University
ClinicalTrials.gov IdentifierNCT01070160
First ReceivedFebruary 16, 2010
Last UpdatedFebruary 26, 2013
Last verifiedFebruary 2013

Tracking Information[ + expand ][ + ]

First Received DateFebruary 16, 2010
Last Updated DateFebruary 26, 2013
Start DateJune 2009
Estimated Primary Completion DateSeptember 2013
Current 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]
Current 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]

Descriptive Information[ + expand ][ + ]

Brief TitleEndometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)
Official TitleEndometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)
Brief Summary
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.
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.
Study TypeObservational
Study PhaseN/A
Study DesignObservational Model: Cohort, Time Perspective: Prospective
ConditionPolycystic Ovarian Syndrome
InterventionDrug: Endometrin (progesterone 100mg vaginal inserts)
once a day, 6-8 days as specified (prior to each EMBx)
Drug: Metformin
per clinical care guidelines
Study Arm (s)
  • A
    Women with PCOS initiating Metformin and exposure to vaginal progesterone for 6-8 days prior ro Endometrium Biopsy
  • B
    Women with PCOS not planning initiating Metformin and exposure to vaginal progesterone for 6-8 days prior to Endometrium Biopsy
  • 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

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment30
Estimated Completion DateSeptember 2013
Estimated Primary Completion DateJuly 2013
Eligibility 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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Lubna Pal, MBBS MRCOG MSc
(203)-737-5619
lubna.pal@yale.edu
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01070160
Other Study ID NumbersU54 HD 052668-02
Has Data Monitoring CommitteeNo
Information Provided ByYale University
Study SponsorYale University
CollaboratorsEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators Principal Investigator: Lubna Pal, MBBS MRCOG MSc Yale University
Verification DateFebruary 2013

Locations[ + expand ][ + ]

Yale-New Haven Hospital Women's Center
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
Recruiting