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Trial record 1 of 1 for:    NCT01427595
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Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenemic Adolescent Girls

This study is currently recruiting participants.
Verified June 2012 by University of Virginia
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: June 12, 2012
Last verified: June 2012
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 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:

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

Contacts
Contact: Michelle Y. Abshire, PhD 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: Michelle Y. Abshire, PhD     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

No publications provided

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: June 12, 2012
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
 Estradiol
Polyestradiol phosphate
Progesterone
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Metformin
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013