Trial record 1 of 13 for:    effects of progesterone on lh AND pcos AND CONTROLS
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Determining How Quickly Progesterone Slows LH Pulse Frequency (CRM001)

This study is currently recruiting participants.
Verified June 2013 by University of Virginia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Chris McCartney, University of Virginia
ClinicalTrials.gov Identifier:
NCT00594217
First received: January 4, 2008
Last updated: June 5, 2013
Last verified: June 2013
  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 will begin E2 patches on day 4-8 of the cycle, while women with PCOS will begin E2 patches either on day 4-8 of the cycle or at least 8 weeks post-menses. After 3 d of E2 administration, women will undergo a 24-h sampling study in the GCRC. Beginning at 2000 h, blood for LH, FSH, E2, P, and T will be obtained over a 24-h period. After 10 h 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 (or after at least 3 weeks in oligomenorrheic PCOS), 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. 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 propose two primary hypotheses: (1) administration of P (at 0600 h) to normally cycling adult women during the follicular phase will result in a demonstrable suppression of daytime LH (and by inference GnRH) pulse frequency within 12 hours; (2) administration of P (at 0600 h) to women with PCOS will result in less suppression of daytime LH pulse frequency than in ovulatory women without PCOS. A secondary hypothesis is that augmentation of LH amplitude after P administration will be less in PCOS compared to normal controls.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
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

Resource links provided by NLM:


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: 72
Study Start Date: November 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
oral micronized P (100 mg p.o.) suspension
Drug: oral micronized P suspension
oral micronized P (100 mg p.o.) suspension
Placebo Comparator: 2
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 in two groups: (1) women with regular menstrual cycles and no evidence of hyperandrogenism, and (2) women with PCOS (defined as clinical/biochemical evidence of hyperandrogenism plus oligomenorrhea, but with no evidence for other endocrinopathies).
  • Subjects will be 18-35 years old.
  • 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.
  • We will exclude women with any other cancer diagnosis and/or treatment (with the exception of basal cell or squamous skin carcinoma) unless they have remained clinically disease free (based on appropriate surveillance) for five years.
  • 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 further 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 (confirmed on repeat) will be excluded, with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome.
  • Abnormal sodium or potassium concentrations (confirmed on repeat); bicarbonate concentrations <20 or >30 (confirmed on repeat)
  • Women with abnormal renal function (i.e., serum creatinine > 1.4) will be excluded (confirmed on repeat)
  • Pregnant and breast-feeding women will be excluded.
  • A history of allergy to progesterone or estradiol will constitute grounds for exclusion.
  • Women with a BMI greater or equal to 40 kg/m2.
  • Virilization
  • A total testosterone > 150 ng/dl in women with PCOS (which suggests the possibility of a virilizing neoplasm) (confirmed on repeat)
  • Elevated DHEAS (mild elevations may be seen in PCOS, and elevations < 1.5 times the upper limit of normal will be accepted in PCOS) (confirmed on repeat)
  • Follicular 17-hydroxyprogesterone > 300 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase and there is a concern about the possibility of congenital adrenal hyperplasia, the 17-hydroxyprogesterone may be collected during the follicular phase, or >60 if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone > 300 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation.
  • A previous diagnosis of diabetes, a fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5%
  • Abnormal TSH (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded; or, for a new diagnosis of hypothyroidism, further study will at the least be delayed pending appropriate treatment) (confirmed on repeat)
  • Abnormal prolactin (mild elevations may be seen in PCOS, and elevations < 1.5 times the upper limit of normal will be accepted in this group) (confirmed on repeat)
  • Evidence of Cushing's syndrome by history or physical exam
  • Due to the amount of blood being drawn in the study, subjects with body weight < 110 lbs. will be excluded from the study
  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: Anne Gabel, BSc 434-243-6911 pcos@virginia.edu

Locations
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Anne Gabel, BSc    434-243-6911    pcos@virginia.edu   
Contact: Christopher McCartney, MD    434-243-6911    cm2hq@virginia.edu   
Principal Investigator: Christopher McCartney, MD         
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Christopher McCartney, MD University of Virginia
  More Information

No publications provided

Responsible Party: Chris McCartney, Associate Professor of Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT00594217     History of Changes
Other Study ID Numbers: 13368, R01HD058671
Study First Received: January 4, 2008
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
PCOS

ClinicalTrials.gov processed this record on April 17, 2014