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

This study is currently recruiting participants.
See Contacts and Locations
Verified December 2016 by Christine Burt Solorzano, University of Virginia
Sponsor:
Information provided by (Responsible Party):
Christine Burt Solorzano, University of Virginia
ClinicalTrials.gov Identifier:
NCT01422746
First received: August 22, 2011
Last updated: December 16, 2016
Last verified: December 2016
  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 adrenocorticotropic hormone (ACTH) or ovarian stimulation testing with recombinant human chorionic gonadotropin (rhCG).

Condition Intervention
Obesity Hyperandrogenemia Polycystic Ovary Syndrome Drug: Metformin

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of Metformin on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess (CBS005)

Resource links provided by NLM:


Further study details as provided by Christine Burt Solorzano, University of Virginia:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
Study Start Date: December 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Metformin
500-1000 mg PO BID (X12 weeks)
Other Name: Glucophage

  Eligibility

Ages Eligible for Study:   7 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01422746

Contacts
Contact: Deborah Sanderson 434-243-6911 pcos@virginia.edu
Contact: Christine Burt Solorzano, MD 434-243-6911 pcos@virginia.edu

Locations
United States, Virginia
University of Virginia Center for Research in Reproduction Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Deborah Sanderson    434-243-6911    pcos@virginia.edu   
Principal Investigator: Christine Burt Solorzano, MD         
Sub-Investigator: John C. Marshall, MD, PhD         
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Christine Burt Solorzano, MD University of Virginia
  More Information

Responsible Party: Christine Burt Solorzano, Assistant Professor of Pediatrics, University of Virginia
ClinicalTrials.gov Identifier: NCT01422746     History of Changes
Other Study ID Numbers: IRB-HSR #19302
CBS006 ( Other Identifier: University of Virginia )
Study First Received: August 22, 2011
Last Updated: December 16, 2016
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Overweight
Polycystic Ovary Syndrome
Hyperandrogenism
Body Weight
Signs and Symptoms
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
Metformin
Androgens
Epinephrine
Racepinephrine
Epinephryl borate
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents

ClinicalTrials.gov processed this record on June 22, 2017