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HypogonadismPhase 2NCT00064987

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

A Phase 2 study testing Testicular biopsy, gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH) in people with Hypogonadism and Kallmann Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Hypogonadism, Kallmann Syndrome
What is being tested?
Testicular biopsy, gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
Apr 2001to Oct 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Prior therapy with gonadotropins (FSH, hCG, or GnRH)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Testicular biopsy, gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH)
Keywords
Male reproduction hormones, Hypogonadotropic hypogonadism, FSH, LH, GnRH
Medical subject headings
Hypogonadism, Kallmann Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Testicular biopsyProcedure or surgery

    Outpatient surgical procedure.

  • gonadotropin releasing hormone (GnRH)Drug

    Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump titrated to reach normal serum testosterone levels)

  • follicle stimulating hormone (FSH)Drug

    Also called Gonal-F

    75 IU subcutaneous injection daily for four months.

Study groups in NCT00064987
Study groupRoleWhat they receive
Group 1 (FSH)ExperimentalPatients 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.
Receives: Procedure: Testicular biopsy; Drug: gonadotropin releasing hormone (GnRH); Drug: follicle stimulating hormone (FSH)
Group 2 (GnRH)Active comparatorPatients 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.
Receives: Procedure: Testicular biopsy; Drug: gonadotropin releasing hormone (GnRH)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. LH

    Average Luteinizing Hormone levels after treatment.

    Measured: month 4 of GnRH treatment

  2. FSH

    Average Follicle Stimulating Hormone levels after treatment.

    Measured: month 4 of GnRH treatment

  3. Testosterone

    Average Testosterone levels after treatment.

    Measured: month 4 of GnRH treatment

  4. Inhibin B

    Average Inhibin B Levels after treatment.

    Measured: month 4 of GnRH treatment

  5. Testicular Size (Volume)

    Average testicular volume after treatment.

    Measured: at baseline and month 4 of GnRH treatment

  6. Sperm Count

    Average sperm count after treatment.

    Measured: month 4 of GnRH treatment

Secondary outcomes (1)

  1. Fertility

    Participants actively seeking to conceive.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2003 (estimated)
  2. Study startApr 2001
  3. Primary completionOct 2012
  4. Study completionOct 2012

Why it stopped: Recruitment was at a standstill. We are currently preparing our results for publication.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00064987
Sponsor's protocol ID
U54HD028138-457
Other IDs
U54HD028138
Status last verified
Jul 2017
First submitted
16 Jul 2003
Last updated
7 Jul 2017
Data monitoring committee
Yes

Publications

  • Pitteloud N, Hayes FJ, Dwyer A, Boepple PA, Lee H, Crowley WF Jr. Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2002 Sep;87(9):4128-36. doi: 10.1210/jc.2002-020518.

    PubMed 12213860

  • Pitteloud N, Hayes FJ, Boepple PA, DeCruz S, Seminara SB, MacLaughlin DT, Crowley WF Jr. The role of prior pubertal development, biochemical markers of testicular maturation, and genetics in elucidating the phenotypic heterogeneity of idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2002 Jan;87(1):152-60. doi: 10.1210/jcem.87.1.8131.

    PubMed 11788640

  • Hayes FJ, Pitteloud N, DeCruz S, Crowley WF Jr, Boepple PA. Importance of inhibin B in the regulation of FSH secretion in the human male. J Clin Endocrinol Metab. 2001 Nov;86(11):5541-6. doi: 10.1210/jcem.86.11.8031.

    PubMed 11701733

  • Kumar PA, Pitteloud N, Andrews PA, Dwyer A, Hayes F, Crowley WF Jr, Dym M. Testis morphology in patients with idiopathic hypogonadotropic hypogonadism. Hum Reprod. 2006 Apr;21(4):1033-40. doi: 10.1093/humrep/dei444. Epub 2006 Jan 5.

    PubMed 16396935

  • Dwyer AA, Sykiotis GP, Hayes FJ, Boepple PA, Lee H, Loughlin KR, Dym M, Sluss PM, Crowley WF Jr, Pitteloud N. Trial of recombinant follicle-stimulating hormone pretreatment for GnRH-induced fertility in patients with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013 Nov;98(11):E1790-5. doi: 10.1210/jc.2013-2518. Epub 2013 Sep 13.

    PubMed 24037890

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Testicular biopsy, gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH) in people with Hypogonadism and Kallmann Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

LH (time frame: month 4 of GnRH treatment). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00064987, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2017.

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