Assessment of Sensitivity of the Hypothalamic GnRH Pulse Generator to Estradiol and Progesterone Inhibition (JCM026)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Virginia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
John Marshall, University of Virginia
ClinicalTrials.gov Identifier:
NCT01428245
First received: August 31, 2011
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

Gonadotropin-releasing hormone (GnRH) is a hormone that regulates the ability of the pituitary to secrete two hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH control the production of female hormones (such as estrogen and progesterone) and the development of eggs by the ovary. Progesterone and estrogen then decrease the number of GnRH pulses produced by the brain (and therefore the number of LH pulses from the pituitary). The ability to decrease GnRH pulses seems to be very important for normal menstrual function in adult women. The purpose of this study is to learn more about how GnRH and LH pulses are controlled during puberty. The information gathered in this study will hopefully allow us to learn more about how menstrual cycles are normally established in girls during puberty.


Condition Intervention
Hyperandrogenemia
Polycystic Ovary Syndrome
Drug: Progesterone
Drug: Estrace (estrogen)

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Assessment of Sensitivity of the Hypothalamic GnRH Pulse Generator to Estradiol and Progesterone Inhibition in Early Pubertal Girls (JCM026)

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • LH Pulse frequency as a function of day 7 progesterone [ Time Frame: 7 days following oral estrace and progesterone administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: January 2009
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Progesterone, estrace

oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr to achieve mean plasma concentrations over the range of 2-8 ng/ml for seven days

oral estrace, 0.5-1 mg once a day for seven days

Drug: Progesterone
oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days
Drug: Estrace (estrogen)
oral estrace, 0.5-1 mg once a day for seven days
Other Name: estradiol

Detailed Description:

In this study, the investigators will aim to discover the effect of 7 days of estrogen and progesterone on GnRH pulses in girls in early and mid puberty. Ultimately, if the investigators understand these normal processes, the investigators may be able to better understand abnormalities of puberty.

  Eligibility

Ages Eligible for Study:   8 Years to 14 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Girls ages 8 to 14
  • Tanner 1-3 pubertal stage
  • Pre-menarchal
  • Normal screening labs

Exclusion Criteria:

  • Abnormal screening labs
  • Congenital adrenal hyperplasia
  • Hyperandrogenism (e.g., hirsutism, elevated free testosterone level)
  • Hemoglobin <12 mg/dL or hematocrit < 36% (Subjects will be offered the opportunity to take iron supplementation for 60 days if their hematocrit is slightly low (33-36%) (suggestive of iron deficiency anemia) and will then return for retesting of their hemoglobin/hematocrit.)
  • Weight < 31 kg
  • History of peanut allergy, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer
  • On hormonal medications (including oral contraceptive pills) or on medications known to affect the reproductive axis within 3 months of the study
  • Pregnant or breast feeding
  • Participation in a research study within the past 30 days that involved taking a study drug.
  • Participation in a research study that involved taking up to or greater than 473 ml's of blood within the past 60 days.
  • Cigarette smoking
  • History of surgery that required bedrest within the past 30 days
  • Family history of hypercoagulability or unexplained thromboembolic disease (not in setting of bedrest, surgery, or malignancy)
  • In order to ensure an adequate number of younger girls, no more than 4 enrolled subjects will be Tanner stage 3
  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: NCT01428245

Contacts
Contact: Anne C Gabel, BSc 434-243-6911 pcos@virginia.edu
Contact: John C Marshall, MD, PhD 434-243-6911 pcos@virginia.edu

Locations
United States, Virginia
Center for Research in Reproduction, University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Anne C Gabel, BSc    434-243-6911    pcos@virginia.edu   
Principal Investigator: John C. Marshall, MD, PhD         
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: John C. Marshall, MD, PhD University of Virginia
  More Information

No publications provided

Responsible Party: John Marshall, Director, Center for Research in Reproduction, University of Virginia
ClinicalTrials.gov Identifier: NCT01428245     History of Changes
Other Study ID Numbers: 14100, U54HD028934-18
Study First Received: August 31, 2011
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Polycystic Ovary Syndrome
Ovarian Cysts
Cysts
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Estradiol
Polyestradiol phosphate
Progesterone
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female
Progestins

ClinicalTrials.gov processed this record on October 16, 2014