- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01427595
Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone
December 14, 2020 updated by: Christine Burt Solorzano, University of Virginia
Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenemic Adolescent Girls (JCM025)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
A better understanding of the factors that make adolescent girls more or less susceptible to the adverse neuroendocrine effects of elevated androgens will hopefully lead to improved prevention and treatment strategies for PCOS.
In this study, we propose to explore the role of hyperinsulinemia on neuroendocrine function in hyperandrogenic adolescent girls by assessing the effect of the insulin sensitizer Metformin on hypothalamic progesterone sensitivity.
Other differences between the progesterone sensitive and progesterone insensitive subgroups, including racial and ethnic differences between the two populations and a trend towards older gynecologic age in the progesterone insensitive population, are being pursued through other ongoing studies (IRB-HSR# 8588 and 12160).
Study Type
Interventional
Enrollment (Actual)
25
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Virginia
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Charlottesville, Virginia, United States, 22908
- Center for Research in Reproduction, University of Virginia
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
8 years to 15 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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)
|
500-2000 mg PO BID (X12 weeks)
oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2)
oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Progesterone Sensitivity Index Before and After Metformin Treatment.
Time Frame: 12 weeks following start of metformin treatment
|
The progesterone (P4) sensitivity index is defined as the percent change in 11-hour LH pulse frequency before and after P4 and estradiol administration for 7 days, divided by the day 7 mean serum P4 concentration.
We compared the P4 sensitivity index after metformin administration to the baseline P4 sensitivity index, using Wilcoxon signed-rank test.
|
12 weeks following start of metformin treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 18, 2009
Primary Completion (Actual)
January 17, 2015
Study Completion (Actual)
January 17, 2015
Study Registration Dates
First Submitted
August 30, 2011
First Submitted That Met QC Criteria
August 31, 2011
First Posted (Estimate)
September 1, 2011
Study Record Updates
Last Update Posted (Actual)
January 8, 2021
Last Update Submitted That Met QC Criteria
December 14, 2020
Last Verified
December 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Endocrine System Diseases
- Ovarian Cysts
- Cysts
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- 46, XX Disorders of Sex Development
- Disorders of Sex Development
- Urogenital Abnormalities
- Adrenogenital Syndrome
- Congenital Abnormalities
- Polycystic Ovary Syndrome
- Hyperandrogenism
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Progestins
- Estradiol
- Metformin
- Progesterone
- Estrogens
Other Study ID Numbers
- 13789
- U54HD028934-18 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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