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Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism

This study has been terminated.
(Recruitment was at a standstill. We are currently preparing our results for publication.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00064987
First Posted: July 17, 2003
Last Update Posted: July 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
William Crowley, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Purpose
Men with idiopathic hypogonadotropic hypogonadism (IHH, Kallmann Syndrome) may have small testicular size, low testosterone levels, no history of puberty, and infertility. These men lack a hormone called gonadotropin releasing hormone (GnRH) that stimulates the development and maturation of the testes. This study will investigate the impact of hormonal treatments on men with IHH. The goal of hormonal therapy is to maximize the potential fertility in these individuals.

Condition Intervention Phase
Hypogonadism Kallmann Syndrome Procedure: Testicular biopsy Drug: gonadotropin releasing hormone (GnRH) Drug: follicle stimulating hormone (FSH) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Role of FSH in Human Gonadal Development

Resource links provided by NLM:


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

Primary Outcome Measures:
  • LH [ Time Frame: month 4 of GnRH treatment ]
    Average Luteinizing Hormone levels after treatment.

  • FSH [ Time Frame: month 4 of GnRH treatment ]
    Average Follicle Stimulating Hormone levels after treatment.

  • Testosterone [ Time Frame: month 4 of GnRH treatment ]
    Average Testosterone levels after treatment.

  • Inhibin B [ Time Frame: month 4 of GnRH treatment ]
    Average Inhibin B Levels after treatment.

  • Testicular Size (Volume) [ Time Frame: at baseline and month 4 of GnRH treatment ]
    Average testicular volume after treatment.

  • Sperm Count [ Time Frame: month 4 of GnRH treatment ]
    Average sperm count after treatment.


Secondary Outcome Measures:
  • Fertility [ Time Frame: 24 months ]
    Participants actively seeking to conceive.


Enrollment: 19
Study Start Date: April 2001
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 (FSH)
Patients in Group 1 will receive subcutaneous follicle stimulating hormone (FSH) injections daily, titrated to achieve a FSH level of 4-8 IU/L, for 4 months. Patients will then receive gonadotropin releasing hormone (GnRH) therapy for 18 months. GnRH will be administered via a portable infusion pump at 2-hour intervals to stimulate endogenous LH secretion.
Procedure: Testicular biopsy
Outpatient surgical procedure.
Drug: gonadotropin releasing hormone (GnRH)
Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump titrated to reach normal serum testosterone levels)
Drug: follicle stimulating hormone (FSH)
75 IU subcutaneous injection daily for four months.
Other Name: Gonal-F
Active Comparator: Group 2 (GnRH)
Patients in Group 2 will receive gonadotropin releasing hormone (GnRH) therapy for 18 months. GnRH will be administered via a portable infusion pump at 2-hour intervals to stimulate endogenous LH secretion. Patients in Group 2 will not receive prior FSH administration.
Procedure: Testicular biopsy
Outpatient surgical procedure.
Drug: gonadotropin releasing hormone (GnRH)
Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump titrated to reach normal serum testosterone levels)

Detailed Description:

Though steroid output of the testes is minimal during childhood, important changes take place that impact spermatogenic potential. Specifically, the number of Sertoli cells increases until testosterone secretion rises during puberty. In animal models, the proliferation of Sertoli cells appears to be regulated by follicle stimulating hormone (FSH) even though FSH levels in childhood are relatively low. At puberty, the number of Sertoli cells becomes fixed; however, the existing cell population then undergoes functional maturation. This switch from proliferation to maturation of Sertoli cells appears to result from rising levels of intratesticular testosterone.

FSH deficiency during testicular development results in decreased numbers of Sertoli cells, even if physiologic hormonal replacement therapy is introduced in adolescence or adulthood. The number of mature Sertoli cells appears to correlate with testicular size, sperm count, and future fertility. An improved understanding of the specific roles of FSH, luteinizing hormone (LH), and testosterone in testicular development may have direct clinical applications in the treatment of male infertility. This study will define the role of FSH in stimulating Sertoli cell proliferation in the human male.

Patients in this study will be randomized to receive either FSH and GnRH (Group 1) or GnRH alone (Group 2). Patients in Group 1 will receive subcutaneous FSH injections daily, titrated to achieve a FSH level of 4-8 IU/L, for 4 months. Patients will then receive GnRH therapy for 18 months. GnRH will be administered via a portable infusion pump at 2-hour intervals to stimulate endogenous LH secretion. Patients in Group 2 will receive the same regimen of exogenous GnRH for 18 months without prior FSH administration.

All patients will undergo an initial assessment that includes an overnight 12-hour frequent blood sampling study, testicular ultrasound, and testicular biopsy. Patients will be followed through monthly study visits with blood tests and seminal fluid analysis. Patients will also have serial testicular ultrasounds to measure testicular growth. Patients in Group 1 will also have a second frequent blood sampling to measure LH, FSH, and testosterone and to confirm the absence of LH pulses.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • no history of spontaneous puberty
  • clinical hypogonadism
  • infantile testes (< 3 ml)
  • no reproductive hormone therapy except testosterone
  • Complete absence of normal LH pulses during 12-hour baseline frequent blood sampling and serum testosterone < 100 ng/dl
  • Normal testing of the anterior pituitary gland
  • Negative MRI of the hypothalamic-pituitary area

Exclusion Criteria

  • Prior therapy with gonadotropins (FSH, hCG, or GnRH)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00064987


Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: William F Crowley, Jr., MD Massachusetts General Hospital
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: William Crowley, Principle Investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00064987     History of Changes
Other Study ID Numbers: U54HD028138-457
U54HD028138 ( U.S. NIH Grant/Contract )
First Submitted: July 16, 2003
First Posted: July 17, 2003
Results First Submitted: April 3, 2017
Results First Posted: July 7, 2017
Last Update Posted: July 7, 2017
Last Verified: July 2017

Keywords provided by William Crowley, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Male reproduction hormones
Hypogonadotropic hypogonadism
FSH
LH
GnRH

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
Follicle Stimulating Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs