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Effect of Metformin on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess

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ClinicalTrials.gov Identifier: NCT01422746
Recruitment Status : Recruiting
First Posted : August 24, 2011
Last Update Posted : August 30, 2019
Sponsor:
Information provided by (Responsible Party):
Christine Burt Solorzano, University of Virginia

Tracking Information
First Submitted Date  ICMJE August 22, 2011
First Posted Date  ICMJE August 24, 2011
Last Update Posted Date August 30, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2016)
Changes in free testosterone or 17-hydroxyprogesterone levels after ACTH and rhCG administration respectively, before and after metformin administration for 12 weeks [ Time Frame: 12 weeks after metformin administration ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 23, 2011)
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 ]
Change History Complete list of historical versions of study NCT01422746 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2016)
Changes in adrenal and ovarian steroid precursors after ACTH and rhCG; 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2011)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Metformin on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess
Official Title  ICMJE 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 adrenocorticotropic hormone (ACTH) or ovarian stimulation testing with recombinant human chorionic gonadotropin (rhCG).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Obesity
  • Hyperandrogenemia
  • Polycystic Ovary Syndrome
Intervention  ICMJE Drug: Metformin
500-1000 mg PO BID (X12 weeks)
Other Name: Glucophage
Study Arms  ICMJE Experimental: metformin
12 weeks metformin, with pre- and post- dexamethasone and ACTH to perform standardized adrenal stimulation testing; dexamethasone and rhCG to perform standardized ovarian stimulation testing
Intervention: Drug: Metformin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 23, 2011)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 luteinizing hormone (LH), lipids, testosterone, prolactin, DHEAS, E2, glucose, and insulin; and decreased follicle-stimulating hormone (FSH) and/or sex hormone-binding globulin (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 polycystic ovary syndrome (PCOS) and adolescent hyperandrogenemia (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 Clinical Research Unit (CRU) 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 7 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Melissa Gilrain 434-243-6911 pcos@virginia.edu
Contact: Christine Burt Solorzano, MD 434-243-6911 pcos@virginia.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01422746
Other Study ID Numbers  ICMJE 19302
CBS006 ( Other Identifier: University of Virginia )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Christine Burt Solorzano, University of Virginia
Study Sponsor  ICMJE University of Virginia
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christine Burt Solorzano, MD University of Virginia
PRS Account University of Virginia
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP