Etiological Factors of Obesity-Associated Hyperandrogenemia in Peripubertal Girls (CRM002)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Virginia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Chris McCartney, University of Virginia
ClinicalTrials.gov Identifier:
NCT00928759
First received: October 28, 2008
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to learn if obese pre- and early pubertal girls with hyperandrogenemia (HA) are more insulin resistant (i.e., have lower insulin-stimulated glucose disposal) compared to obese peripubertal girls without HA; and that overnight mean luteinizing hormone (LH) concentration is also an independent predictor of free testosterone concentrations, especially in mid- to late pubertal girls.


Condition
Obesity
Hyperandrogenemia
Polycystic Ovary Syndrome

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Etiological Factors of Obesity-Associated Hyperandrogenemia in Peripubertal Girls

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Morning free testosterone [ Time Frame: 0700 to 0900 hours ] [ Designated as safety issue: No ]
  • Insulin-stimulated glucose disposal [ Time Frame: 0900 to 1100 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Estimated 24-hour mean insulin concentration [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Luteinizing hormone pulse frequency [ Time Frame: 1800 to 0900 hours ] [ Designated as safety issue: No ]
  • Mean luteinizing hormone concentration [ Time Frame: 1800 to 0900 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: March 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
peripubertal obese girls
Peripubertal obese girls, aged 8 - 16 years, who are obese (BMI-for-age percentile greater or equal to 95)

Detailed Description:

A number of pathophysiological mechanisms underlie the polycystic ovary syndrome (PCOS). Neuroendocrine abnormalities play a significant role in most women with PCOS, and PCOS is associated with relative resistance of the gonadotropin releasing hormone (GnRH) pulse generator to negative feedback by progesterone and estradiol. This hypothalamic resistance to negative feedback appears to be a result of hyperandrogenemia (HA), and can also occur in adolescents with HA. We have hypothesized that peripubertal HA (which can represent a forerunner of adult PCOS) can promote the development of PCOS in part via induction of hypothalamic resistance to negative feedback. However, the cause of peripubertal HA remains largely unknown. Obesity is a well-recognized pathophysiological factor in the HA of adult PCOS; and recent data demonstrate that peripubertal obesity is associated with HA. However, the mechanisms underlying the relationship between peripubertal obesity and HA—and the marked variability of androgen levels observed among obese girls—are unknown. We have gathered preliminary data that suggests that obese pre- and early pubertal girls with high androgen levels also exhibit greater degrees of insulin resistance compared to obese girls with lower androgens.

The primary goal of this pilot project is to begin to establish the relationship between insulin resistance (as determined by insulin clamp studies) and free testosterone concentrations in obese peripubertal girls. Secondarily, the aim is to assess the contributions of elevated luteinizing hormone (determined by frequent blood sampling for LH) in obesity-associated HA across puberty.

Subjects will be admitted to the General Clinical Research Center at 1600 h after 4 hours of fasting. We will measure luteinizing hormone every 10 minutes from 1800 h to 0900 h; other hormones (e.g., testosterone) will be assessed as well. Measurements of insulin and glucose will occur before and after a standardized mixed meal (eaten at 1900 h) and while fasting the following morning. A standard hyperinsulinemic euglycemic clamp procedure will be performed from 0900-1100 h.

Characterization of the factors underlying peripubertal HA may permit prediction of which pre- and early pubertal girls will subsequently go on to develop symptoms of PCOS. Data generated by this project will prompt novel future studies to investigate the complex interactions among metabolic and classical endocrine pathways that lead to PCOS.

  Eligibility

Ages Eligible for Study:   8 Years to 16 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Generally healthy peripubertal girls ages 8 - 16 years with a BMI of > or = to 95th percentile will be recruited from the general population of the surrounding area.

Criteria

Inclusion Criteria:

  • Peripubertal (Tanner stage 1 to 5) girl, age 8-16 years
  • Obesity (BMI-for-age ≥ 95th percentile)
  • Generally healthy (save for exogenous obesity)
  • Ability and willingness of subject/parents to provide informed assent/consent

Exclusion Criteria:

  • Age < 8 or > 16 y
  • Greater than 4 y post-menarche
  • Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc.
  • Pregnancy or lactation
  • Virilization
  • Total testosterone > 150 ng/dl, which suggests the possibility of a virilizing neoplasm
  • DHEAS greater than twice upper limit of age-appropriate normal range
  • 17-OHP greater than 250 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if postmenarcheal, the 17-OHP will be collected during the follicular phase, or > 60 if oligomenorrheic) NOTE: If a 17-OHP > 250 ng/dl is confirmed on repeat testing, an ACTH stimulation test will be offered, with a post-ACTH 17-OHP < 1000 ng/dl being required for study participation
  • History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8)
  • Fasting glucose > 125 mg/dl or hemoglobin A1c > 7.0%
  • Abnormal TSH or prolactin
  • Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth, striae)
  • Hematocrit < 36% or hemoglobin < 12 g/dl
  • Significant and current cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring systemic intermittent corticosteroids; etc.)
  • Abnormal liver enzymes, age-specific alkaline phosphatase, or a bilirubin > 1.5 times upper limit of normal
  • Abnormal sodium, potassium, bicarbonate concentrations, or elevated creatinine concentration
  • Weight less than 34 kg is an exclusion criterion (to ensure safe blood withdrawal)
  • Subjects using restricted medication (see restrictions below) are excluded unless the subject's primary care provider approves stopping the medication
  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: NCT00928759

Contacts
Contact: Anne Gabel, BSc 434-243-6911 pcos@virginia.edu
Contact: Christopher McCartney, MD 434-243-6911 cm2hq@virginia.edu

Locations
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Anne Gabel, BSc    434-243-6911    pcos@virginia.edu   
Principal Investigator: Christopher McCartney, MD         
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Christopher McCartney, MD University of Virginia
  More Information

No publications provided

Responsible Party: Chris McCartney, Associate Professor of Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT00928759     History of Changes
Other Study ID Numbers: 13552
Study First Received: October 28, 2008
Last Updated: January 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Virginia:
Obesity
Polycystic Ovary Syndrome

Additional relevant MeSH terms:
Obesity
Polycystic Ovary Syndrome
Syndrome
Hyperandrogenism
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Disease
Pathologic Processes
46, XX Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Adrenogenital Syndrome
Congenital Abnormalities

ClinicalTrials.gov processed this record on September 22, 2014