- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00351416
Letrozole Treatment in Normal and GnRH Deficient Women
This research study involves the use of the drugs Letrozole, GnRH, and NAL-GLU GnRH antagonist. Letrozole is a drug that is approved by the U.S. Food and Drug Administration (FDA) for use in breast cancer treatment that has been found to block the formation of estrogen. The NAL-GLU GnRH antagonist is a drug that temporarily blocks the action of GnRH. GnRH is a hormone that the body makes that stimulates other hormones that then control the function of the ovary.
The purpose is to study the effects of the administration of letrozole in women with GnRH deficiency at the same time that they receive gonadotropin-releasing hormone (GnRH). In addition, administration of letrozole and NAL-GLU GnRH antagonist in healthy women with normal menstrual cycles will be done to evaluate the role of estrogen in the control of the hormone FSH, or Follicle Stimulating Hormone, in the female reproductive cycle. A better understanding of FSH control may help in the development of new treatments for women with difficulty conceiving.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The negative feedback control of FSH is crucial for the precise regulation of follicular development in the female. An important component of this feedback is exerted by estrogen. Letrozole will be used to block aromatase and therefore estradiol production in normal and GnRH deficient females. These studies will dissect the relative roles of estradiol and inhibin on FSH secretion at the pituitary and hypothalamus.
The aromatase inhibitors block aromatization of androgens to estrogens, allowing us to examine the relative contribution of estradiol and the inhibins to FSH regulation. The use of a submaximal dose of a GnRH antagonist will allow us to estimate the overall amount of GnRH secreted (hypothalamic contribution) with and without aromatase inhibition.
A more thorough understanding of estrogen and inhibin feedback on FSH will improve our understanding of the failure of follicle development in subsets of patients with infertility, such as polycystic ovary syndrome, in which FSH levels are normal but follicles fail to develop. Study of FSH control will also help us understand the failure of negative feedback on FSH, which can result in multiple follicular development and multiple gestation and its associated costs and risks. Thus, these studies may afford new therapeutic options for conception in infertile patients while simultaneously providing new methods to avoid the risks of multiple gestations.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02114
- Reproductive Endocrine Unit, Massachusetts General Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Healthy Normal Subjects will meet the following criteria:
- 18 to 35 years of age
- good general health
- on no medications including any hormonal drug products for at least 3 months before the study
- regular menstrual cycles every 25-35 days with ovulation documented by a luteal phase progesterone > 3 ng/ml
- no evidence of androgen excess
- normal TSH, prolactin and hemoglobin
- use of double-barrier contraception, permanent sterilization or abstinence during the cycle of study.
- Negative pregnancy test (serum) at the beginning of each cycle of study
- Normal Liver Function Test
Exclusion Criteria:
- History of liver and/or kidney disease
- Substance or alcohol abuse
- Hormone dependent neoplasia including breast cancer
- Women who are trying to become pregnant
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Aromatase inhibitor EFP
Letrozole administration (20 mg) on day 2-4 (EFP; early follicular phase) of cycle 2 and Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. |
Letrozole 20 mg orally one time
Other Names:
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
Other Names:
|
Experimental: Aromatase inhibitor LFP
Letrozole administration (20 mg daily x 2) at follicle size of > 16 mm (LFP; late follicular phase) in cycle 2. Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. |
Letrozole 20 mg orally one time
Other Names:
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
FSH Level
Time Frame: EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm
|
Difference in FSH peak following letrozole administration compared with control cycle
|
EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary 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
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Letrozole
- Aromatase Inhibitors
- LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-
Other Study ID Numbers
- 2003-P-001895
- Sundry Department Fund (Other Identifier: MGH-REU Department Fund)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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