Effect of Metformin on Sensitivity of the Gonadotropin-releasing Hormone (GnRH) Pulse Generator to Suppression by Estradiol and Progesterone

The recruitment status of this study is unknown because the information has not been verified recently.

Verified December 2013 by University of Virginia.
Recruitment status was Recruiting

Sponsor:

Collaborator:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Information provided by (Responsible Party):

John Marshall, University of Virginia

ClinicalTrials.gov Identifier:

NCT01427595

First received: August 30, 2011

Last updated: December 9, 2013

Last verified: December 2013

History of Changes

Purpose

Many, but not all, girls with high levels of the male hormone testosterone go on to develop polycystic ovary syndrome (PCOS) as adults. Women with PCOS often have irregular menstrual periods, excess facial and body hair, and weight gain. PCOS is also a leading cause of difficulty becoming pregnant. The investigators do not understand why some girls with high hormones develop PCOS and others do not. In a previous study by our group, some girls with high levels of male hormones had abnormalities in the secretion of another hormone, called luteinizing hormone (LH), that are often seen in women with PCOS. However, another group had normal LH secretion. The girls with the abnormal LH secretion had higher levels of another hormone, called insulin, than the girls with normal LH secretion. The investigators will test whether metformin, an insulin-sensitizing agent, changes the effects of high male hormone levels in adolescent girls, specifically by looking at their LH secretion response following metformin treatment.

Condition	Intervention
Polycystic Ovary Syndrome Hyperandrogenism	Drug: Metformin Drug: Progesterone Drug: estrace


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenemic Adolescent Girls (JCM025)

Resource links provided by NLM:

Genetics Home Reference related topics: 17 alpha-hydroxylase/17,20-lyase deficiency 21-hydroxylase deficiency 3-beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency persistent Müllerian duct syndrome

MedlinePlus related topics: Hormones Polycystic Ovary Syndrome

Drug Information available for: Estradiol Progesterone Estradiol cypionate Metformin Estradiol valerate Metformin hydrochloride Estradiol acetate Estradiol hemihydrate

Genetic and Rare Diseases Information Center resources: 21-hydroxylase Deficiency Congenital Adrenal Hyperplasia

U.S. FDA Resources

Further study details as provided by University of Virginia:

Primary Outcome Measures:

Change in LH pulse frequency before and after Metformin treatment. [ Time Frame: 12 weeks following start of metformin treatment ] [ Designated as safety issue: No ]
The primary aim will be to compare the change in 11-hour LH pulse frequency between the 1st and the 2nd admissions (Δ(2-1)) to the change in the 11-hour LH pulse frequency between the 3rd and the 4th admissions (Δ(4-3)).


Estimated Enrollment:	30
Study Start Date:	July 2008
Estimated Study Completion Date:	April 2015
Estimated Primary Completion Date:	April 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Metformin, progesterone , estrace 12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X)	Drug: Metformin 500-2000 mg PO BID (X12 weeks) Drug: Progesterone oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2) Drug: estrace oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2

Eligibility


Ages Eligible for Study:	10 Years to 17 Years (Child)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Girls ages 10 to 17
Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the mean for normal control subjects of the same Tanner Stage)
Creatinine clearance > 90 ml/min as calculated by the Cockcroft-Gault equation
Hemoglobin > 12 mg/dL or Hematocrit > 36%
Normal screening labs (with exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
Sexually active subjects must agree to abstain or use double barrier contraception during the study
Subjects must agree not to take any other medications during the course of the study without approval by the study investigators.

Exclusion Criteria:

Abnormal screening labs (with the exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
Creatinine clearance less than 90 ml/min as calculated by Cockcroft-Gault equation
Hemoglobin <12 mg/dL or hematocrit < 36%
Abnormal liver function tests, including Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Bilirubin, Albumin, and Alkaline Phosphatase
Weight < 34 kg
History of renal dysfunction, liver dysfunction, congestive heart failure, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer
Pregnant or breast feeding
On medications known to affect the reproductive axis within 3 months of the study (including oral contraceptive pills, metformin, and spironolactone)
Are currently participating in another study or have been in one in the last 30 days.
Subjects using restricted medication (see restrictions below) are excluded unless the subject's primary care provider approves stopping the medication.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01427595

Contacts


Contact: Anne C Gabel, BSc	434-243-6911	pcos@virginia.edu
Contact: John C. Marshall, MD, PhD	434-243-6911	pcos@virginia.edu

Locations


United States, Virginia
Center for Research in Reproduction, University of Virginia	Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Anne C Gabel, BSc 434-243-6911 pcos@virginia.edu
Principal Investigator: John C. Marshall, MD, PhD

Sponsors and Collaborators

University of Virginia

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators


Principal Investigator:	John C. Marshall, MD, PhD	University of Virginia

More Information


Responsible Party:	John Marshall, Director, Center for Research in Reproduction, University of Virginia
ClinicalTrials.gov Identifier:	NCT01427595 History of Changes
Other Study ID Numbers:	13789 U54HD028934-18
Study First Received:	August 30, 2011
Last Updated:	December 9, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by University of Virginia:


hyperandrogenemia

Additional relevant MeSH terms:


Polycystic Ovary Syndrome Hyperandrogenism Ovarian Cysts Cysts Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Gonadal Disorders Endocrine System Diseases 46, XX Disorders of Sex Development Disorders of Sex Development Urogenital Abnormalities Adrenogenital Syndrome Congenital Abnormalities	Metformin Estradiol Polyestradiol phosphate Progesterone Estradiol 3-benzoate Estradiol 17 beta-cypionate Estradiol valerate Hypoglycemic Agents Physiological Effects of Drugs Estrogens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Progestins Contraceptive Agents Reproductive Control Agents

ClinicalTrials.gov processed this record on September 23, 2016

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