- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01428193
Effects of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone
Effect of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenic Adolescent Girls (JCM021)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Similar to women with PCOS, girls with hyperandrogenemia have an increased frequency of LH pulses when compared to age matched controls. An ongoing study by our group is investigating whether the progesterone insensitivity of the GnRH pulse generator in adult women with PCOS is also seen in adolescent girls with hyperandrogenemia. Analysis of the data to date suggests that the hyperandrogenic adolescent girls have decreased hypothalamic progesterone sensitivity when compared to adolescent controls, with a subgroup (consisting of approximately half of the hyperandrogenic girls) having marked progesterone insensitivity similar to that seen in adult women with PCOS. These data have recently been published.
Given that androgens mediate hypothalamic progesterone insensitivity in adult women with PCOS, we hypothesize that androgens play a similar role in adolescent girls with hyperandrogenemia and that progesterone sensitivity can be restored with the use of the androgen receptor blocker flutamide.
Better understanding the effects of hyperandrogenemia in adolescence and its role in the development of PCOS will hopefully lead to improved prevention and treatment strategies for PCOS. This may prove increasingly important if the current epidemic in childhood obesity results in a growing number of girls with elevated androgen levels.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Virginia
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Charlottesville, Virginia, United States, 22908
- Center for Research in Reproduction, University of Virginia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Girls ages 13 to 17
- Tanner IV or V stage of puberty
- Post-menarche
- Hyperandrogenemic (total testosterone > 0.4 ng/mL or free testosterone > 35 pmol/L) with or without hirsutism
- Normal aspartate aminotransferase/alanine aminotransferase (AST/ALT) (AST < 35 U/L, ALT < 55 U/L)
- Hemoglobin > 12 mg/dL or Hematocrit > 36%
- Normal screening labs (with exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
- Sexually active subjects must agree to abstain or use double barrier contraception during the study
- Subjects must agree not to take any other medications during the course of the study without approval by the study investigators
Exclusion Criteria:
- Abnormal screening labs (with the exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
- Elevated AST/ALT (AST > 35 U/L, ALT > 55 U/L)
- Hemoglobin <12 mg/dL or hematocrit < 36%
- Weight < 32 kg
- History of liver disease, peanut allergy, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer
- Pregnant or breastfeeding
- On medications known to affect the reproductive axis within 3 months of the study (including oral contraceptive pills, metformin, and spironolactone)
- On medications known or likely to inhibit or induce CYP1A2 or CYP3A4 (please see "Restrictions on use of other drugs or treatments" section below for common examples of such drugs)
- Are currently participating in another study or have been in one in the last 30 days.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Flutamide, estrace, progesterone
For flutamide, subjects weighing > 50 kg will receive 250 mg orally twice a day, and subjects weighing < 50 kg will receive 125 mg orally twice a day for approximately 3 weeks. Subjects will be given oral estrace, 0.5-1 mg once a day for 7 days following the first overnight study admission. Subjects will be given oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days following the first overnight study admission. |
Subjects weighing > 50 kg will receive 250 mg orally twice a day, and subjects weighing < 50 kg will receive 125 mg orally twice a day.
oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days
0.5-1 mg once a day for seven days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Slope of the Percent Change in Luteinizing Hormone (LH) Pulses as a Function of Day 7 Progesterone Level
Time Frame: 3 weeks after flutamide treatment
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The primary outcome variable for the study is the slope of the percent change in LH pulses as a function of day 7 progesterone level.
|
3 weeks after flutamide treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Christopher R. McCartney, MD, University of Virginia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Endocrine System Diseases
- Ovarian Cysts
- Cysts
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- 46, XX Disorders of Sex Development
- Disorders of Sex Development
- Urogenital Abnormalities
- Adrenogenital Syndrome
- Congenital Abnormalities
- Polycystic Ovary Syndrome
- Hyperandrogenism
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Estrogens
- Hormone Antagonists
- Androgen Antagonists
- Progestins
- Estradiol
- Progesterone
- Flutamide
Other Study ID Numbers
- 12632
- U54HD028934-18 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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