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

NCT01422746 | Unknown Early Phase 1 DMC FDA Drug

• 2 other identifiers: 19302CBS006
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Changes in free testosterone or 17-hydroxyprogesterone levels after ACTH and rhCG administration respectively, before and after metformin administration for 12 weeks

  12 weeks after metformin administration

Secondary Outcomes (1)

• 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

  12 weeks after metformin administration

Study Arms (1)

metformin

EXPERIMENTAL

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

Interventions

Metformin DRUG

500-1000 mg PO BID (X12 weeks)

Also known as: Glucophage

metformin

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia Center for Research in Reproduction

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Polycystic Ovary Syndrome

Interventions

Metformin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Christine Burt Solorzano, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Gilrain

CONTACT

434-243-6911; pcos@virginia.edu

Christine Burt Solorzano, MD

CONTACT

434-243-6911; pcos@virginia.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: August 22, 2011
• First Posted: August 24, 2011
• Study Start: March 20, 2017
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: October 27, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)