Sleep-wake Changes of Luteinizing Hormone Frequency in Pubertal Girls With and Without High Testosterone (CRM005)

This study is currently recruiting participants.
Verified January 2013 by University of Virginia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Chris McCartney, University of Virginia
ClinicalTrials.gov Identifier:
NCT00930007
First received: June 24, 2009
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to determine whether sleep-wake changes of luteinizing hormone pulse frequency are different in early pubertal girls with high testosterone levels compared to early pubertal girls with normal testosterone levels.


Condition
Hyperandrogenism

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Comparison of Sleep-wake LH Frequency in Peripubertal Girls With and Without Hyperandrogenemia

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Luteinizing hormone pulse frequency (while awake and while asleep) [ Time Frame: Baseline (time zero) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progesterone concentration [ Time Frame: Baseline (time zero) ] [ Designated as safety issue: No ]
  • Estradiol concentration [ Time Frame: Baseline (time zero) ] [ Designated as safety issue: No ]
  • Testosterone concentrations [ Time Frame: Baseline (time zero) ] [ Designated as safety issue: No ]
  • Luteinizing hormone amplitude [ Time Frame: Baseline (time zero) ] [ Designated as safety issue: No ]
  • Sleep stage parameters [ Time Frame: Baseline (time zero) ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Serum obtained during frequent sampling will be stored (in case repeat measurements are required), but will be discarded at the end of the study


Estimated Enrollment: 90
Study Start Date: October 2008
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Hyperandrogenemic
Girls with elevated free testosterone concentrations
Controls
Girls with normal free testosterone concentrations

Detailed Description:

During early puberty, luteinizing hormone (LH) pulse frequency normally increases during sleep. In contrast, preliminary data suggest that obese girls (who have high testosterone levels in general) demonstrate low LH frequency during the day and night during early puberty; but at mid puberty rapidly transition to a high LH frequency during the day and night. We hypothesize that in early pubertal girls with high testosterone levels, overnight increases of LH frequency are less prominent than those observed in early pubertal girls with normal testosterone levels. We will assess this using a frequent sampling protocol for assessment of LH pulse frequency (with sampling occurring while awake and while asleep) in early pubertal girls with and without high testosterone levels. Sleep will be formally evaluated.

  Eligibility

Ages Eligible for Study:   8 Years to 15 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Community sample and patients from local clinics

Criteria

Inclusion Criteria:

  • Early to midpubertal girls (late Tanner 1 [i.e., estradiol > 20 pg/ml] to Tanner 3)
  • Premenarcheal
  • Approximate ages, 8-15 years

Exclusion Criteria:

  • BMI-for-age < 5th percentile
  • Inability to comprehend what will be done during the study or why it will be done
  • Being a study of GnRH pulse regulation in adolescent girls with and without HA, boys are excluded
  • 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 (confirmed on repeat)
  • DHEAS > upper limit of age-appropriate normal range (confirmed on repeat) (mild elevations may be seen in adolescent HA, and elevations < 1.5 times the age-appropriate upper limit of normal will be accepted in such girls)
  • Follicular phase 17-hydroxyprogesterone > 250 ng/dl (for girls < 12 years old) or > 300 ng/dl (for girls 12 and older) (confirmed on repeat), which suggests the possibility of congenital adrenal hyperplasia. NOTE: If an elevated follicular 17-hydroxyprogesterone is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation
  • History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8)
  • A previous diagnosis of diabetes
  • Fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5% (confirmed on repeat)
  • Abnormal TSH (confirmed on repeat) (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded)
  • Abnormal prolactin (confirmed on repeat) (mild elevations may be seen in HA girls, and elevations < 1.5 times the upper limit of normal will be accepted in this group)
  • Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth in children, striae)
  • Hematocrit < 36% and hemoglobin < 12 g/dl (confirmed on repeat)
  • Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)
  • Persistent liver test abnormalities (confirmed on repeat), with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome
  • Persistently abnormal sodium, potassium, or elevated creatinine concentration (confirmed on repeat)
  • Bicarbonate concentrations < 20 or > 30 (confirmed on repeat)
  • No medications known to affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure can be taken in the 3 months prior to the first inpatient GCRC study (or in the 2 months prior to screening)

    • Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, psychotropics, and sympathomimetics/stimulants (e.g., methylphenidate)
    • Patients taking restricted medications will be excluded unless written permission (for the subjects to discontinue the medication) is received from the subject's physician
  • Weight < 22 kg is an absolute exclusion criterion (to ensure safe blood withdrawal)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00930007

Contacts
Contact: Anne Gabel 434-243-6911 am7bd@virginia.edu

Locations
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Anne Gabel    434-243-6911    am7bd@virginia.edu   
Principal Investigator: Christopher R McCartney, MD         
Sub-Investigator: Paul Suratt, MD         
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Christopher R McCartney, MD University of Virginia
  More Information

No publications provided

Responsible Party: Chris McCartney, Associate Professor of Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT00930007     History of Changes
Other Study ID Numbers: 13950, R01HD058671
Study First Received: June 24, 2009
Last Updated: January 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Virginia:
Luteinizing hormone
Puberty

Additional relevant MeSH terms:
Adrenogenital Syndrome
Hyperandrogenism
46, XX Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Gonadal Disorders
Endocrine System Diseases
Testosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014