Recruiting
Early Phase 1

Metformin

Sponsor:

University of Virginia

Code:

NCT01422746

Conditions

Obesity

Hyperandrogenemia

Polycystic Ovary Syndrome

Eligibility Criteria

Sex: Female

Age: 7 - 18

Healthy Volunteers: Not accepted

Interventions

Metformin

Study Details

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).

Conditions

Obesity

Hyperandrogenemia

Polycystic Ovary Syndrome

Study ID

NCT01422746

Start date

Mar 20, 2017

Status verified date

Oct, 2023

Completion date

Dec, 2024

Anticipated

Primary completion date

Dec, 2024

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 7 - 18

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

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

Interventions

Metformin

500-1000 mg PO BID (X12 weeks)

Primary outcome measure

  • 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 ]

Central Contacts and Locations

Central contacts

Melissa Gilrain

434-243-6911pcos@virginia.edu

Christine Burt Solorzano, MD

434-243-6911pcos@virginia.edu

Locations

University of Virginia Center for Research in Reproduction

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Melissa Gilrain

434-243-6911pcos@virginia.edu

Principal Investigator:

Christine Burt Solorzano, MD

More Information

Sponsor

University of Virginia

Last update posted

Oct 27, 2023

Last verified

Oct, 2023

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Virginia on 2023-10-27.