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

Polycystic Ovarian Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01070160
• Other study ID #: 0905005203
• Secondary ID: U54HD052668-02
• Status: Completed
• Start date: June 2009
• Est. completion date: July 2013

Study information

• Verified date: June 2014
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

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

Related Conditions & MeSH terms

• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• Endometrin (progesterone 100mg vaginal inserts)
once a day, 6-8 days as specified (prior to each EMBx)
• Metformin
per clinical care guidelines

Locations

Country	Name	City	State
United States	Yale-New Haven Hospital Women's Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		baseline
Primary	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		3 months
Primary	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		9 months
Secondary	blood draw (20mL)		on day of EMBx
Secondary	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		9 months

External Links

•   Drug Information available for: Endometrin (progesterone vaginal)
•   Drug Information available for: Metformin
•   MedlinePlus related topics: Polycystic Ovary Disease