Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02705014

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To investigate the hormone response of hypothalamic-pituitary-gonad axis and spermatogenesis in male pituitary stalk interruption syndrome patients by pulsatile GnRH therapy.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadotropic Hypogonadism	Drug: Gonadotropin-releasing Hormone	N/A

Detailed Description

To investigate the hormone response of hypothalamic-pituitary-gonad axis and spermatogenesis in male pituitary stalk interruption syndrome patients by pulsatile GnRH therapy. The hormonal response of the hypothalamic-pituitary-gonad axis was assessed after pulsatile GnRH replacement by measurement of serum T, LH and FSH. A standard seminal fluid analysis was performed in men who could produce an ejaculate.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Aug 1, 2016

Anticipated Study Completion Date :

Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment group patients were administered with pulsatile gonadotropin-releasing hormone (GnRH )therapy for 12 months at an interval of 90 minutes.The GnRH dosage was initially 10ug per pulse and was progressively adjusted to maintain serum testosterone levels at 6.94-17.35 nmol/L.	Drug: Gonadotropin-releasing Hormone A regimen of pulsatile GnRH (Fengyuan pharmaceutical company, Anhui province, China) administered subcutaneous via a portable infusion pump (Weichuang Medical Science Company, Shanghai city, China) at a 90-minute interval. The GnRH dosage was initially 10ug per pulse and was progressively adjusted to maintain serum testosterone levels at 6.94-17.35 nmol/L ( 200-500 ng/dL). Other Names: Gonadorelin

Arm

Intervention/Treatment

Experimental: treatment group

patients were administered with pulsatile gonadotropin-releasing hormone (GnRH )therapy for 12 months at an interval of 90 minutes.The GnRH dosage was initially 10ug per pulse and was progressively adjusted to maintain serum testosterone levels at 6.94-17.35 nmol/L.

Drug: Gonadotropin-releasing Hormone

A regimen of pulsatile GnRH (Fengyuan pharmaceutical company, Anhui province, China) administered subcutaneous via a portable infusion pump (Weichuang Medical Science Company, Shanghai city, China) at a 90-minute interval. The GnRH dosage was initially 10ug per pulse and was progressively adjusted to maintain serum testosterone levels at 6.94-17.35 nmol/L ( 200-500 ng/dL).

Other Names:

Gonadorelin

Outcome Measures

Primary Outcome Measures

Change of serum Luteinizing Hormone(LH) value [Baseline and at 1m,3m, 6m, 9m and 12m post treatment.]
Luteinizing hormone (LH) is measured using commercial kits by chemiluminescent method (ACS 180 Automatic Chemiluminescence System; Bayer). Reference range: 1.24-8.62 IU/L. Initial efficacy is evaluated based on the values of serum LH and serum total testosterone. If a subject's serum LH value below 1.5 IU/L and serum total testosterone value below 100 ng/dL at 3m post treatment, it is defined as failure to pulsatile GnRH treatment and continuous treatment is stopped. Otherwise, pulsatile GnRH treatment is continued.
Change of serum Follicle-Stimulating Hormone (FSH) value [Baseline and at 1m,3m, 6m, 9m and 12m post treatment.]
Follicle-stimulating hormone (FSH) are measured using commercial kits by chemiluminescent method (ACS 180 Automatic Chemiluminescence System; Bayer). Reference range: 1.27-19.26 IU/L.
Change of serum total testosterone value [Baseline and at 1m,3m, 6m, 9m and 12m post treatment.]
Total testosterone levels are measured using commercial kits by chemiluminescent method (ACS 180 Automatic Chemiluminescence System; Bayer). Reference range: 175-781 ng/dL.Initial efficacy is evaluated based on the values of serum LH and serum totaltestosterone. If a subject's serum LH value below 1.5 IU/L and serum total testosterone value below 100 ng/dL at 3m post treatment, it is defined as failure to pulsatile GnRH treatment and continuous treatment is stopped. Otherwise, pulsatile GnRH treatment is continued.

Secondary Outcome Measures

Change of testicular volume [Baseline and at 1m,3m, 6m, 9m and 12m post treatment]
Testicular volumes are measured using Prader orchidometer. Prader orchidometer is a standard method to measure testicular volume. The normal range of testicular volume of each side in normal adult men is 15-25ml.
Change of sperm counts by routine semen analysis [Baseline and at 3m, 6m, 9m and 12m post treatment]
if a subject can produce an ejaculate, semen samples are collected by masturbation and analyzed according to the standard World Health Organization method.
the rate of impregnating subject's wife [at 3m, 6m, 9m and 12m post treatment]
For subjects who have sex partners, pregnancies are documented according to subjects' reports after treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

18 years or over male patients;
Absent or incomplete puberty development;
Serum testosterone values below 3.47 nmol/L by low or normal serum LH and FSH concentrations.
at least two or more pituitary hormone deficiencies
Brain MRI showed absent and thin pituitary stalk, or pituitary hypoplasia and/or ectopic posterior pituitary.