Letrozole Treatment in Normal and GnRH Deficient Women

Healthy Volunteers Clinical Trial

Official title:

Letrozole Treatment in Normal and GnRH Deficient Women

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00351416
• Other study ID #: 2003-P-001895
• Secondary ID: Sundry Departmen
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: July 10, 2006
• Last updated: November 5, 2013
• Start date: July 2004
• Est. completion date: December 2018

Study information

• Verified date: November 2013
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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 inhibin to FSH regulation. Using normal subjects and GnRH-deficient subjects receiving replacement GnRH allows us to compare the effect of relative estradiol blockade at the pituitary (GnRH deficient subjects) vs the pituitary and hypothalamus (normal subjects), thus determining the direct site of estradiol action.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: December 2018
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

GnRH Deficient Subjects will meet the following criteria:

• 18 to 40 years of age

• good general health

• on no gonadal replacement for at least 1 month before the study

• GnRH deficiency (idiopathic hypogonadotropic hypogonadism or Kallmann's Syndrome, secondary hypothalamic amenorrhea, acquired hypogonadotropic hypogonadism)

• normal TSH, prolactin and hemoglobin

• use of double-barrier contraception or abstinence during the cycle of Letrozole administration

• 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 Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteers
• Hypogonadism
• Hypogonadotropic Hypogonadism
• Kallmann Syndrome
• Kallmann's Syndrome

Intervention

Drug:
• Letrozole
Letrozole 20mg orally one time
• NAL-GLU GnRH antagonist
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
• GnRH
For GnRH-deficient subjects only: 75 ng/kg GnRH IV

Locations

Country	Name	City	State
United States	Reproductive Endocrine Unit, Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In healthy subjects, the acute changes in FSH, inhibin A, inhibin B and estradiol between the Letrozole and control cycles at each cycle stage		end of control and treatment cycles	No
Primary	The average LH, FSH, inhibin A, inhibin B, estradiol and progesterone in the control and treatment cycles		end of control and treatment cycles	No
Primary	The number of pulses in 8 hrs and LH pulse amplitude will be compared in the control and treatment cycle		after each 16-hour admission	No
Primary	The percent suppression of LH will be compared in the control and Letrozole cycles		after each 16-hour admission	No