Determining the Rapidity With Which Exogenous P Suppresses Daytime LH (GnRH) Pulse Frequency in Women During the Follicular Phase of the Menstrual Cycle - Full Text View

Sponsors and Collaborators:	University of Virginia Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	University of Virginia
ClinicalTrials.gov Identifier:	NCT00594217

Purpose

The rapidity with which Progesterone (P) suppresses daytime lutenizing hormone (LH) (and by inference gonadotropin releasing hormone (GnRH)) pulse frequency is unknown. We propose to assess this further using a randomized, cross-over, placebo-controlled study. Ovulatory women pretreated with estradiol (E2) will undergo a 24-hour sampling study in the General Clinical Research Center (GCRC). After 10 hours of sampling, either oral micronized progesterone (100 mg p.o.) suspension or placebo suspension will be administered (according to randomization). During a subsequent menstrual cycle, subjects will undergo another GCRC study identical to the first (including pretreatment with E2) except that oral progesterone will be exchanged for placebo or vice versa in accordance with the crossover design. We will assess the acute effects of progesterone on LH frequency, with secondary endpoints being mean LH, LH pulse amplitude, and mean follicle-stimulating hormone (FSH). We hypothesize that administration of P (at 0600 h) to adult women during the follicular phase will result in a demonstrable suppression of daytime LH (and by inference GnRH) pulse frequency within 12 hours.

Ovulatory women will begin E2 (estradiol) patches on day 4-8 of the cycle. On day 7-11 of the study cycle (i.e., after 3 days of E2 administration), women will undergo a 24-hr sampling study in the General Clinical Research Center. Beginning at 2000 hr, blood for LH (lutenizing hormone), FSH (follicle-stimulating hormone), E2 (estradiol), P (progesterone), and T (testosterone) will be obtained over a 24-hour period. After 10 hours of sampling, either oral micronized P (100 mg p.o.) suspension or placebo suspension will be administered (according to randomization). At the completion of sampling, E2 patches will be discontinued. During a subsequent menstrual cycle, subjects will undergo another GCRC study identical to the first (including pretreatment with E2) except that oral P will be exchanged for placebo or vice versa in accordance with the crossover design.

Hypothesis to be Tested: Administration of P (at 0600 h) to adult women during the follicular phase will result in a demonstrable suppression of daytime LH (and by inference GnRH) pulse frequency within 12 hours. We will also assess the acute effects of P on mean LH, LH pulse amplitude, and mean FSH.

Condition	Intervention
PCOS	Drug: oral micronized P suspension Other: Placebo

MedlinePlus related topics: Menstruation

Drug Information available for: Gonadorelin Gonadorelin hydrochloride LH-RH

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Determining the Rapidity With Which Exogenous P Suppresses Daytime LH (GnRH) Pulse Frequency in Women During the Follicular Phase of the Menstrual Cycle

Further study details as provided by University of Virginia:

Primary Outcome Measures:

The primary endpoint is the change in the number of LH pulses (over 10 h) attributable to Progesterone. [ Time Frame: 10 hours before and after administration of micronized progesterone and placebo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

acute effects of P on mean LH [ Time Frame: 10 hours before and after administration of micronized progesterone and placebo ] [ Designated as safety issue: No ]
acute effects of P on mean LH pulse amplitude [ Time Frame: 10 hours before and after administration of micronized progesterone and placebo ] [ Designated as safety issue: No ]
acute effects of P on mean FSH [ Time Frame: 10 hours before and after administration of micronized progesterone and placebo ] [ Designated as safety issue: No ]

Estimated Enrollment:	33
Study Start Date:	November 2007
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental oral micronized P (100 mg p.o.) suspension	Drug: oral micronized P suspension oral micronized P (100 mg p.o.) suspension
2: Placebo Comparator Placebo	Other: Placebo Placebo

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Subjects will be healthy women with regular menstrual cycles and no evidence of hyperandrogenism.
Subjects will have no significant health problems and will have normal screening biochemical blood test results.
Subjects will be 18-35 years old; we use a cutoff age of 35 years because early menopause at this age is very rare, and the risk of DVT with estrogen use may increase beyond this age.
Subjects will be willing to strictly avoid pregnancy (using non-hormonal methods) during the time of study and must be willing and able to provide informed consent.

Exclusion Criteria:

We will exclude women with a history of any disorders that may potentially be complicated by hormonal treatment, such as DVT and breast, ovarian, or endometrial cancer.
Women with anemia (hematocrit < 36% and/or a hemoglobin level <12 g/dl) will be treated with iron for a maximum of 2 sequential months before the 1st admission and/or before the 2nd admission. If they remain anemic after 2 sequential months of ferrous gluconate (325 mg bid), they will then be excluded from participation in the study.
Women with a history of any disorders that may potentially be complicated by long-term iron supplementation, such as hemochromatosis and polycythemia vera, will be excluded.
Women with a significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; known or suspected coronary atherosclerosis; asthma requiring systemic intermittent corticosteroids; etc.) will be excluded.
Women with liver enzymes, alkaline phosphatase, or bilirubin > 1.5 times upper limit of normal will be excluded.
Women with abnormal renal function (i.e., serum creatinine > 1.4) will be excluded.
Pregnant and breast-feeding women will be excluded.
A history of allergy to progesterone (which is extremely rare), estradiol, or iron supplements will constitute grounds for exclusion.
Women with a BMI greater or equal to 30 kg/m2.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594217

Contacts

Contact: Christopher McCartney, MD	434-243-6911	cm2hq@virginia.edu
Contact: Lauren Lockhart	434-243-6911	lsa5s@virginia.edu

Locations

United States, Virginia
University of Virginia	Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Lauren Lockhart 434-243-6911 lsa5s@virginia.edu
Contact: Christopher McCartney, MD 434-243-6911 cm2hq@virginia.edu
Principal Investigator: Christopher McCartney, MD

Sponsors and Collaborators

University of Virginia

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:

Christopher McCartney, MD

University of Virginia

More Information

Responsible Party:	University of Virginia ( Christopher McCartney, MD )
Study ID Numbers:	13368
Study First Received:	January 4, 2008
Last Updated:	August 6, 2008
ClinicalTrials.gov Identifier:	NCT00594217
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Virginia:

PCOS

ClinicalTrials.gov processed this record on January 16, 2009