Letrozole Treatment in Normal and GnRH Deficient Women

NCT00351416 | Unknown Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2003-P-001895Sundry Department Fund
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

GnRH deficiency; GnRH antagonist; Letrozole; GnRH; FSH; LH; Inhibins

Outcome Measures

Primary Outcomes (1)

• FSH Level

  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

Study Arms (2)

Aromatase inhibitor EFP

EXPERIMENTAL

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.

Drug: Letrozole; Drug: NAL-GLU GnRH antagonist

Aromatase inhibitor LFP

EXPERIMENTAL

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.

Drug: Letrozole; Drug: NAL-GLU GnRH antagonist

Interventions

Letrozole DRUG

Letrozole 20 mg orally one time

Also known as: aromatase inhibitor, Femara

Aromatase inhibitor EFP; Aromatase inhibitor LFP

NAL-GLU GnRH antagonist DRUG

5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously

Also known as: GnRH antagonist

Aromatase inhibitor EFP; Aromatase inhibitor LFP

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Normal Subjects will meet the following criteria:
• 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

You may not qualify if:

• History of liver and/or kidney disease
• Substance or alcohol abuse
• Hormone dependent neoplasia including breast cancer
• Women who are trying to become pregnant

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Reproductive Endocrine Unit, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Interventions

Letrozole; Aromatase Inhibitors; LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Results Point of Contact

• Title: Janet Hall
• Organization: Massachusetts General Hospital

jehall@partners.org

617-877-1112

Study Officials

• Janet E Hall, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician

Model Details: This is a physiologic study designed to investigate the relative roles of estradiol and inhibin A or inhibin B in the control of FSH secretion during normal menstrual cycles using an aromatase inhibitor. Subjects serve as their own control with no intervention in cycle 1 and letrozole administration in cycle 2. Subjects are studied in the early follicular phase or the late follicular phase.

Study Record Dates

• First Submitted: July 10, 2006
• First Posted: July 12, 2006
• Study Start: January 21, 2004
• Primary Completion: June 29, 2009
• Last Updated: July 27, 2017
• Results First Posted: April 27, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)