Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome
Primary Purpose
Hypogonadotropic Hypogonadism
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Gonadotropin-releasing Hormone
Sponsored by
About this trial
This is an interventional treatment trial for Hypogonadotropic Hypogonadism focused on measuring pituitary stalk interruption syndrome, pulsatile GnRH therapy, hypogonadotropic hypogonadism, hypopituitarism
Eligibility Criteria
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.
Exclusion Criteria:
- cryptorchidism history
- other causes of hypopituitarism or severe systemic disease
Sites / Locations
- Peking Union Medical College HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
treatment group
Arm Description
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.
Outcomes
Primary Outcome Measures
Change of serum Luteinizing Hormone(LH) value
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
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
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
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
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
For subjects who have sex partners, pregnancies are documented according to subjects' reports after treatment.
Full Information
NCT ID
NCT02705014
First Posted
February 22, 2016
Last Updated
March 6, 2016
Sponsor
Peking Union Medical College Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02705014
Brief Title
Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome
Official Title
Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Unknown status
Study Start Date
January 2016 (undefined)
Primary Completion Date
August 2016 (Anticipated)
Study Completion Date
August 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadotropic Hypogonadism
Keywords
pituitary stalk interruption syndrome, pulsatile GnRH therapy, hypogonadotropic hypogonadism, hypopituitarism
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
treatment group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Gonadotropin-releasing Hormone
Other Intervention Name(s)
Gonadorelin
Intervention Description
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).
Primary Outcome Measure Information:
Title
Change of serum Luteinizing Hormone(LH) value
Description
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.
Time Frame
Baseline and at 1m,3m, 6m, 9m and 12m post treatment.
Title
Change of serum Follicle-Stimulating Hormone (FSH) value
Description
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.
Time Frame
Baseline and at 1m,3m, 6m, 9m and 12m post treatment.
Title
Change of serum total testosterone value
Description
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.
Time Frame
Baseline and at 1m,3m, 6m, 9m and 12m post treatment.
Secondary Outcome Measure Information:
Title
Change of testicular volume
Description
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.
Time Frame
Baseline and at 1m,3m, 6m, 9m and 12m post treatment
Title
Change of sperm counts by routine semen analysis
Description
if a subject can produce an ejaculate, semen samples are collected by masturbation and analyzed according to the standard World Health Organization method.
Time Frame
Baseline and at 3m, 6m, 9m and 12m post treatment
Title
the rate of impregnating subject's wife
Description
For subjects who have sex partners, pregnancies are documented according to subjects' reports after treatment.
Time Frame
at 3m, 6m, 9m and 12m post treatment
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Exclusion Criteria:
cryptorchidism history
other causes of hypopituitarism or severe systemic disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xue-yan Wu
Email
wuxueyan@pumch.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xue-yan Wu
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25131486
Citation
Shao WM, Bai WJ, Chen YM, Liu L, Wang YJ. [Micropump infusion of gonadorelin in the treatment of hypogonadotropic hypogonadism in patients with pituitary stalk interruption syndrome: cases analysis and literature review]. Beijing Da Xue Xue Bao Yi Xue Ban. 2014 Aug 18;46(4):642-5. Chinese.
Results Reference
result
PubMed Identifier
28368486
Citation
Zheng J, Mao J, Xu H, Wang X, Huang B, Liu Z, Cui M, Xiong S, Ma W, Min L, Kaiser UB, Nie M, Wu X. Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2291-2300. doi: 10.1210/jc.2016-3990.
Results Reference
derived
Learn more about this trial
Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome
We'll reach out to this number within 24 hrs