Effect of Metformin on Sensitivity of the Gonadotropin-releasing Hormone (GnRH) Pulse Generator to Suppression by Estradiol and Progesterone
Overview[ - collapse ][ - ]
| 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 | Polycystic Ovary Syndrome Hyperandrogenism |
| Intervention | Drug: Metformin Drug: Progesterone Drug: estrace |
| Phase | N/A |
| Sponsor | University of Virginia |
| Responsible Party | University of Virginia |
| ClinicalTrials.gov Identifier | NCT01427595 |
| First Received | August 30, 2011 |
| Last Updated | December 9, 2013 |
| Last verified | December 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | August 30, 2011 |
|---|---|
| Last Updated Date | December 9, 2013 |
| Start Date | July 2008 |
| Estimated Primary Completion Date | April 2015 |
| Current 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)). |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Effect of Metformin on Sensitivity of the Gonadotropin-releasing Hormone (GnRH) Pulse Generator to Suppression by Estradiol and Progesterone |
|---|---|
| Official Title | Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenemic Adolescent Girls (JCM025) |
| Brief Summary | 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. |
| Detailed Description | Not Provided |
| Study Type | Interventional |
| Study Phase | N/A |
| Study Design | Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science |
| Condition |
|
| Intervention | 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 |
| Study Arm (s) | 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) |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 30 |
| Estimated Completion Date | April 2015 |
| Estimated Primary Completion Date | April 2015 |
| Eligibility 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. |
| Gender | Female |
| Ages | 10 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Anne C Gabel, BSc 434-243-6911 pcos@virginia.edu |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01427595 |
|---|---|
| Other Study ID Numbers | 13789 |
| Has Data Monitoring Committee | No |
| Information Provided By | University of Virginia |
| Study Sponsor | University of Virginia |
| Collaborators | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
| Investigators | Principal Investigator: John C. Marshall, MD, PhD University of Virginia |
| Verification Date | December 2013 |
Locations[ + expand ][ + ]
| Center for Research in Reproduction, University of Virginia | Charlottesville, Virginia, United States, 22908 Contact: Anne C Gabel, BSc | 434-243-6911 | pcos@virginia.eduPrincipal Investigator: John C. Marshall, MD, PhD Recruiting |
|---|