Effect of Metformin on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess
Overview[ - collapse ][ - ]
| Purpose | This study will test whether metformin administration can ameliorate androgen (male hormone) overproduction in overweight pubertal girls with androgen excess. The investigators hypothesize that improvement in insulin sensitivity by 12 weeks of metformin administration will improve androgen levels after adrenal stimulation testing with ACTH or ovarian stimulation testing with recombinant human chorionic gonadotropin (r-hCG). |
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| Condition | Obesity Hyperandrogenemia Polycystic Ovary Syndrome |
| Intervention | Drug: Metformin Drug: Dexamethasone Drug: Cosyntropin Drug: r-hCG (Ovidrel) |
| Phase | N/A |
| Sponsor | University of Virginia |
| Responsible Party | University of Virginia |
| ClinicalTrials.gov Identifier | NCT01422746 |
| First Received | August 22, 2011 |
| Last Updated | June 12, 2012 |
| Last verified | June 2012 |
Tracking Information[ + expand ][ + ]
| First Received Date | August 22, 2011 |
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| Last Updated Date | June 12, 2012 |
| Start Date | Not Provided |
| Estimated Primary Completion Date | Not Provided |
| Current Primary Outcome Measures | Changes in free testosterone or 17 OH progesterone levels after ACTH and r-hCG administration respectively, before and after metformin administration for 12 weeks [Time Frame: 12 weeks after metformin administration] [Designated as safety issue: No] |
| Current Secondary Outcome Measures | Changes in adrenal and ovarian steroid precursors after ACTH and r-hCG; body composition via air displacement plethysmography, BMI, and glucose tolerance testing results; baseline and after 12 weeks of metformin administration [Time Frame: 12 weeks after metformin administration] [Designated as safety issue: No] |
Descriptive Information[ + expand ][ + ]
| Brief Title | Effect of Metformin on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess |
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| Official Title | Effect of Metformin on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess (CBS005) |
| Brief Summary | This study will test whether metformin administration can ameliorate androgen (male hormone) overproduction in overweight pubertal girls with androgen excess. The investigators hypothesize that improvement in insulin sensitivity by 12 weeks of metformin administration will improve androgen levels after adrenal stimulation testing with ACTH or ovarian stimulation testing with recombinant human chorionic gonadotropin (r-hCG). |
| 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 |
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| Intervention | Drug: Metformin 500-1000 mg PO BID (X12 weeks) Drug: Dexamethasone 1 mg PO twice Drug: Cosyntropin 250 micrograms IV twice Drug: r-hCG (Ovidrel) 25 mcg IV twice |
| Study Arm (s) | Experimental: metformin, dexamethasone, Cosyntropin (ACTH), r-hCG 12 weeks metformin, Dexamethasone and ACTH to perform standardized adrenal stimulation testing, dexamethasone and r-hCG to perform standardized ovarian stimulation testing |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Not yet recruiting |
|---|---|
| Estimated Enrollment | 20 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | Not Provided |
| Eligibility Criteria | Inclusion Criteria: - overweight(>85th BMI%) females - Early to late puberty (expected age range 7-18) - Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the mean for normal control subjects of the same Tanner Stage) - Screening labs within age-appropriate normal range, with the exception of a mildly low hematocrit (see below) and the hormonal abnormalities inherent in obesity which could include mildly elevated LH, lipids, testosterone, prolactin, DHEAS, E2, glucose, and insulin and decreased FSH and/or SHBG Exclusion Criteria: - Age < 7 or > 18 y - Inability to comprehend what will be done during the study or why it will be done - BMI-for-age < 5th percentile - Positive pregnancy test or lactation. - Abnormal laboratory studies will be confirmed by repeat testing to exclude laboratory error. - Morning cortisol < 3 µg/dL or history of Cushing syndrome or adrenal insufficiency - History of congenital adrenal hyperplasia or 17-hydroxyprogesterone > 300 ng/dL, which suggests the possibility of congenital adrenal hyperplasia (if postmenarcheal, the 17-hydroxyprogesterone will be collected during the follicular phase, or ≥ 40 days since last menses if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone >300 mg/dL is confirmed on repeat testing, an ACTH-stimulated 17-hydroxyprogesterone <1000 ng/dL will be required for study participation. - Total testosterone > 150 ng/dL, which suggests the possibility of a virilizing neoplasm - DHEAS greater than the upper limit of age-appropriate normal range (mild elevations may be seen in PCOS and adolescent HA, and elevations < 1.5 times the age-appropriate upper limit of normal will be accepted in these groups) - Virilization - Previous diagnosis of diabetes, fasting glucose ≥126 mg/dL, or a hemoglobin A1c ≥6.5% - Abnormal thyroid stimulating hormone (TSH) for age. Subjects with stable and adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded. - Abnormal prolactin. Mild elevations may be seen in overweight girls, and elevations <1.5 times the upper limit of normal will be accepted in this group. - Persistent hematocrit <36% and hemoglobin <12 g/dL. Subjects with a mildly low hematocrit (33-36%) will be asked to take iron in the form of ferrous gluconate for up to 60 days. Subjects weighing ≤ 36 kg will take one 300-325 mg tablet oral ferrous gluconate daily (containing 36 mg elemental iron);subjects weighing >36 kg will take two 300-325 mg tablets oral ferrous gluconate daily (containing 36 mg elemental iron each). They will return to the CRC after 30-60 days of iron therapy to have their hemoglobin or hematocrit rechecked and will proceed with the remainder of the study if it is ≥12 g/dL or ≥36%, respectively. - Persistent liver test abnormalities, with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Mild elevations may be seen in overweight girls, so elevations <1.5 times the upper limit of normal will be accepted in this group. - Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.) - Abnormal sodium, potassium, or bicarbonate concentrations, or elevated creatinine concentration (confirmed on repeat) - No medications known to affect the reproductive system or glucose metabolism can be taken in the 3 months prior to the study. Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, and psychotropics. |
| Gender | Female |
| Ages | 7 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Michelle Y. Abshire, PhD 434-243-6911 pcos@virginia.edu |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01422746 |
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| Other Study ID Numbers | CBS005 |
| Has Data Monitoring Committee | No |
| Information Provided By | University of Virginia |
| Study Sponsor | University of Virginia |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Christine Burt Solorzano, MD University of Virginia |
| Verification Date | June 2012 |
Locations[ + expand ][ + ]
| University of Virginia Center for Research in Reproduction | Charlottesville, Virginia, United States, 22908 Contact: Michelle Y. Abshire, PhD | 434-243-6911 | pcos@virginia.eduPrincipal Investigator: Christine Burt Solorzano, MD Not yet recruiting |
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