Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Information provided by (Responsible Party):
William Crowley, National Institute of Child Health and Human Development
ClinicalTrials.gov Identifier:
NCT00493961
First received: June 28, 2007
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

Men with Idiopathic Hypogonadotropic Hypogonadism (IHH) lack a hormone called gonadotropin releasing hormone (GnRH). This hormone is important for starting puberty, maintaining testosterone levels, and fertility. The purpose of this study is to research the effects of treating IHH men with GnRH for 7 days.


Condition Intervention
Kallmann Syndrome
Idiopathic Hypogonadotropic Hypogonadism
GnRH Deficiency
Drug: gonadotropin releasing hormone (GnRH)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of 7 Days of Exogenous Pulsatile GnRH Treatment on the Pituitary-Gonadal Axis in Hypogonadotropic Hypogonadal Subjects

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • testosterone [ Time Frame: daily for 7 days ] [ Designated as safety issue: No ]
  • LH [ Time Frame: frequent sampling for 2 hours ] [ Designated as safety issue: No ]
  • FSH [ Time Frame: frequent sampling for 2 hours ] [ Designated as safety issue: No ]
  • Inhibin B [ Time Frame: daily for 7 days ] [ Designated as safety issue: No ]
  • free alpha subunit [ Time Frame: daily for 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: January 1999
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: gonadotropin releasing hormone (GnRH)
    Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump)
Detailed Description:

Despite variability in the triggers, timing, and pace of sexual maturity between species, all species utilize the final pathway of hypothalamic secretion of gonadotropin releasing hormone (GnRH) to initiate and maintain the reproductive axis. Thus, GnRH is required for reproductive competence in the human. The classic studies from the 1970s clearly demonstrate that pulsatile release of GnRH from the hypothalamus is a prerequisite for physiologic gonadotrope function. Absence, decreased frequency or decreased amplitude of pulsatile GnRH release results in the clinical syndrome of hypogonadotropic hypogonadism (HH). The phenotypic expression of GnRH deficiency in the human demonstrates considerable heterogeneity. Defining the physiology of GnRH is critical to understanding the clinical heterogeneity of isolated GnRH deficiency and its comparison to other conditions resulting in hypogonadotropic hypogonadism (HH). The overall goal of this protocol is to investigate the neuroendocrine control of reproduction and specifically the physiology and pathophysiology of GnRH secretion and action in the human male.

Subjects will be selected from a group of adult men (18-65 years)based on the demonstration of a low testosterone level (<100 ng/dL) in association with low or inappropriately normal gonadotropin levels. All patients will undergo an initial assessment that includes an overnight 12-hour frequent blood sampling study to determine their degree of endogenous GnRH secretion. Following the overnight evaluation, subjects will have daily outpatient visits for 7 consecutive days when they will receive a GnRH bolus followed by 2hrs of blood sampling.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of idiopathic hypogonadotropic hypogonadism (IHH) or Kallmann syndrome (KS)Adult male 18-65 years of age
  • Serum testosterone <100 ng/dL

Exclusion Criteria:

  • No specific exclusion criteria
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493961

Contacts
Contact: Ravikumar Balasubramanian, MD, PhD 617-726-8432 rbalasubramanian@mgh.harvard.edu
Contact: Nirav Patel, BA 617-726-1896 npatel34@mgh.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114-2696
Contact: Ravikumar Balasubramanian, MD, PhD    617-726-8432    rbalasubramanian@mgh.harvard.edu   
Contact: Nirav Patel, BA    617-726-1896    npatel34@mgh.harvard.edu   
Sub-Investigator: Paul A Boepple, MD         
Sub-Investigator: Frances J Hayes, MD         
Sub-Investigator: Nelly Pitteloud, MD         
Sub-Investigator: Stephanie B Seminara, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Ravikumar Balasubramanian, MD, PhD    617-726-8432    rbalasubramanian@mgh.harvard.edu   
Contact: Nirav Patel, BA    617-726-1896    npatel34@mgh.harvard.edu   
Sponsors and Collaborators
William Crowley
Investigators
Principal Investigator: William F Crowley, Jr., MD Massachusetts General Hospital
  More Information

Additional Information:
Publications:

Responsible Party: William Crowley, Professor, National Institute of Child Health and Human Development
ClinicalTrials.gov Identifier: NCT00493961     History of Changes
Other Study ID Numbers: U54HD028138-447
Study First Received: June 28, 2007
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Kallmann Syndrome
Idiopathic Hypogonadotropic Hypogonadism
GnRH deficiency

Additional relevant MeSH terms:
Kallmann Syndrome
Hypogonadism
Gonadal Disorders
Endocrine System Diseases
46, XY Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014