Time Course of Waking Versus Sleep-associated Luteinizing Hormone (LH) Pulse Frequency Suppression in Response to Progesterone in Late Pubertal Girls With and Without Hyperandrogenemia (CRM003)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by University of Virginia
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Chris McCartney, University of Virginia
ClinicalTrials.gov Identifier:
First received: June 23, 2009
Last updated: May 10, 2016
Last verified: May 2016
The purpose of this study is to determine if in late pubertal girls without hyperandrogenemia (HA), progesterone (P) will acutely reduce waking lutenizing hormone (LH) frequency to a greater extent than sleep-associated LH frequency. We hypothesize that in late pubertal girls with HA: (a) waking and sleep-associated LH frequency will be elevated (compared to controls); and (b) P will suppress waking LH frequency to a lesser degree than it does in girls without HA.

Condition Intervention
Drug: Micronized progesterone suspension
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: Time Course of Waking vs. Sleep-associated LH Pulse Frequency Suppression in Response to Progesterone in Late Pubertal 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 [ Time Frame: Baseline and 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progesterone [ Time Frame: Baseline and 2 months ] [ Designated as safety issue: No ]
  • Testosterone [ Time Frame: Baseline and 2 months ] [ Designated as safety issue: No ]
  • Estradiol [ Time Frame: Baseline and 2 months ] [ Designated as safety issue: No ]
  • Luteinizing hormone pulse amplitude [ Time Frame: Baseline and 2 months ] [ Designated as safety issue: No ]
  • Sleep parameters (e.g., sleep stages) [ Time Frame: Baseline and 2 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: June 2008
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Progesterone
Micronized progesterone suspension
Drug: Micronized progesterone suspension
micronized progesterone 0.8 mg/kg at 0700, 1500 2300 and 0700
Placebo Comparator: Placebo
Drug: Placebo

Detailed Description:
During early puberty, LH frequency increases during sleep; but in late puberty, LH frequency decreases overnight. Nonetheless, nocturnal LH frequency is similar (~0.5 pulses per hour) in early and late pubertal girls. Preliminary data in early pubertal girls suggests that progesterone acutely slows waking LH frequency, but does not acutely change nocturnal LH frequency. We hypothesize that daytime LH frequency is regulated primarily by sex steroid negative feedback, while sleep-associated LH frequency is not; and that androgens interfere with sex steroid suppression of daytime LH frequency. We propose to assess this further using a protocol in which short-term Progesterone and placebo is given to late pubertal girls (in a cross-over fashion), with subsequent assessment of LH pulse frequency (with sampling occurring while awake and while asleep). We propose that any effect of Progesterone will be blunted or absent in late pubertal girls with hyperandrogenemia.

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Late pubertal girls (Tanner breast stage 3, 4, or 5)
  2. Postmenarcheal, but no more than 4 y postmenarcheal
  3. Age 10-17 y

Exclusion Criteria:

  1. Age < 10 or > 17 y
  2. BMI-for-age < 5th percentile
  3. Inability to comprehend what will be done during the study or why it will be done
  4. Being a study of GnRH pulse regulation in adolescent girls with and without HA, boys are excluded
  5. Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc.
  6. Pregnancy or lactation
  7. Virilization
  8. Total testosterone > 150 ng/dl
  9. DHEAS > upper limit of age-appropriate normal range (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)
  10. 17-hydroxyprogesterone > 250 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if postmenarcheal, the 17-hydroxyprogesterone will be collected during the follicular phase, or >60 if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone > 250 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation
  11. History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8)
  12. A previous diagnosis of diabetes
  13. Fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5% (confirmed on repeat)
  14. Abnormal TSH (confirmed on repeat) (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded)
  15. 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)
  16. Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth in children, striae)
  17. Hematocrit < 36% and hemoglobin < 12 g/dl (specifically, documentation of a hematocrit >= 36% or a hemoglobin >= 12 g/dl in the month prior to GCRC admission is required for the frequent sampling protocol in the GCRC)
  18. Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)
  19. 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
  20. Persistently abnormal sodium, potassium, or elevated creatinine concentration (confirmed on repeat)
  21. Bicarbonate concentrations < 20 or > 30 (confirmed on repeat)
  22. 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.
  23. Weight < 22 kg is an absolute exclusion criterion (to ensure safe blood withdrawal)
  24. Personal history of deep venous thrombosis (DVT)
  25. Personal history of ovarian, endometrial, or breast neoplasia
  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: NCT00929006

Contact: Debbie Sanderson 434-243-6911 pcos@virginia.edu

United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Debbie Sanderson    434-243-6911    pcos@virginia.edu   
Principal Investigator: Christopher McCartney, MD         
Sponsors and Collaborators
University of Virginia
National Institutes of Health (NIH)
Principal Investigator: Christopher R McCartney, M D University of Virginia
  More Information

Responsible Party: Chris McCartney, Associate Professor of Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT00929006     History of Changes
Other Study ID Numbers: 13717 
Study First Received: June 23, 2009
Last Updated: May 10, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
polycystic ovary syndrome

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

ClinicalTrials.gov processed this record on May 26, 2016