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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:
Information provided by (Responsible Party):
William Crowley, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00064987
First received: July 16, 2003
Last updated: April 1, 2014
Last verified: April 2014

July 16, 2003
April 1, 2014
April 2001
October 2012   (final data collection date for primary outcome measure)
  • LH [ Time Frame: weekly & monthly ] [ Designated as safety issue: No ]
  • FSH [ Time Frame: weekly & monthly ] [ Designated as safety issue: No ]
  • testosterone [ Time Frame: weekly & monthly ] [ Designated as safety issue: No ]
  • Inhibin B [ Time Frame: weekly & monthly ] [ Designated as safety issue: No ]
  • testicular size (volume) [ Time Frame: monthly ] [ Designated as safety issue: No ]
  • sperm count [ Time Frame: monthly ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00064987 on ClinicalTrials.gov Archive Site
Fertility [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism
Role of FSH in Human Gonadal Development

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hypogonadism
  • Kallmann Syndrome
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
14
October 2012
October 2012   (final data collection date for primary outcome measure)

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)
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00064987
U54HD028138-457
Yes
William Crowley, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
Principal Investigator: William F Crowley, Jr., MD Massachusetts General Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP