NCT00064987

Brief 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. 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Apr 2001

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2001

Completed
2.3 years until next milestone

First Submitted

Initial submission to the registry

July 16, 2003

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 17, 2003

Completed
9.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2012

Completed
4.8 years until next milestone

Results Posted

Study results publicly available

July 7, 2017

Completed
Last Updated

July 7, 2017

Status Verified

July 1, 2017

Enrollment Period

11.5 years

First QC Date

July 16, 2003

Results QC Date

April 3, 2017

Last Update Submit

July 5, 2017

Conditions

HypogonadismKallmann Syndrome

Keywords

Male reproduction hormonesHypogonadotropic hypogonadismFSHLHGnRH

Outcome Measures

Primary Outcomes (6)

  • LH

    Average Luteinizing Hormone levels after treatment.

    month 4 of GnRH treatment

  • FSH

    Average Follicle Stimulating Hormone levels after treatment.

    month 4 of GnRH treatment

  • Testosterone

    Average Testosterone levels after treatment.

    month 4 of GnRH treatment

  • Inhibin B

    Average Inhibin B Levels after treatment.

    month 4 of GnRH treatment

  • Testicular Size (Volume)

    Average testicular volume after treatment.

    at baseline and month 4 of GnRH treatment

  • Sperm Count

    Average sperm count after treatment.

    month 4 of GnRH treatment

Secondary Outcomes (1)

  • Fertility

    24 months

Study Arms (2)

Group 1 (FSH)

EXPERIMENTAL

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 biopsyDrug: gonadotropin releasing hormone (GnRH)Drug: follicle stimulating hormone (FSH)

Group 2 (GnRH)

ACTIVE COMPARATOR

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 biopsyDrug: gonadotropin releasing hormone (GnRH)

Interventions

Testicular biopsyPROCEDURE

Outpatient surgical procedure.

Group 1 (FSH)Group 2 (GnRH)
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)

Group 1 (FSH)Group 2 (GnRH)
follicle stimulating hormone (FSH)DRUG

75 IU subcutaneous injection daily for four months.

Also known as: Gonal-F
Group 1 (FSH)

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (5)

  • 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.

    PMID: 12213860BACKGROUND

  • 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.

    PMID: 11788640BACKGROUND

  • 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.

    PMID: 11701733BACKGROUND

  • 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.

    PMID: 16396935BACKGROUND

  • 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.

    PMID: 24037890DERIVED

MeSH Terms

Conditions

HypogonadismKallmann Syndrome

Interventions

Gonadotropin-Releasing HormoneFollicle Stimulating Hormonefollitropin alfa

Condition Hierarchy (Ancestors)

Gonadal DisordersEndocrine System DiseasesDisorder of Sex Development, 46,XYDisorders of Sex DevelopmentUrogenital AbnormalitiesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing HormonesHypothalamic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNeuropeptidesPeptidesAmino Acids, Peptides, and ProteinsOligopeptidesNerve Tissue ProteinsProteinsGonadotropins, PituitaryGonadotropinsPituitary Hormones, AnteriorPituitary Hormones

Results Point of Contact

Title
Dr. William Crowley
Organization
Massachusetts General Hospital
wcrowley@partners.org
617-724-2470

Study Officials

  • William F Crowley, Jr., MD

    Massachusetts General Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principle Investigator

Study Record Dates

First Submitted

July 16, 2003

First Posted

July 17, 2003

Study Start

April 1, 2001

Primary Completion

October 1, 2012

Study Completion

October 1, 2012

Last Updated

July 7, 2017

Results First Posted

July 7, 2017

Record last verified: 2017-07

Locations

US(1)