Back to resultsEfficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH) (IHH)
Primary Purpose
Isolated Hypogonadotropic Hypogonadism, Kallmann Syndrome, Infertility
Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Human Chorionic Gonadotropin
human menopausal gonadotropin
Sponsored by
About this trial
This is an interventional treatment trial for Isolated Hypogonadotropic Hypogonadism focused on measuring Gonadotropin treatment, human chorionic gonadotropin, human menopausal gonadotropin
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18, ≤ 45 years old;
- Adolescent dysplasia or loss of puberty: Genital Tanner score ﹤ 5, pubic hair Tanner score ﹤ 5;
- Serum FSH and LH levels are low or in normal low value, testosterone was lower than normal range (1.75ng / ml, the lower limit of the normal blood testosterone reference range of Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology);
- With or without olfactory loss/reduction;
- Other pituitary hormone levels are normal;
- Head MRI examination is normal;
- Fertility is desired currently or will be desired in the future;
- Understand and sign the informed consent form.
Exclusion Criteria:
- Primary hypogonadism;
- Acquired hypogonadotrophic hypogonadism;
- A history of treatment with pulsed GnRH, hCG and FSH related hormones;
- Receive testosterone replacement therapy for more than 6 months;
- History of cryptorchidism or cryptorchidism;
- The sperm density before treatment ≥1×10^6/ml;
- Moderate or severe liver and kidney dysfunction (ALT>120IU/L, AST>80IU/L, CR>115μmol/L);
- The karyotype is 45,X or 47,XXY and 48, XXXY and other abnormal karyotypes;
- True hermaphroditism and pseudohermaphroditism;
- Sex hormone abnormalities caused by adrenal lesions;
- Hypogonadism secondary to other systemic diseases;
- Abnormal secretion of hormones caused by brain lesions (such as pituitary tumors);
- There are other hormone abnormalities in the pituitary;
- There are contraindications for the treatment with hCG or hMG.
Sites / Locations
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Human Chorionic Gonadotropin alone
hCG alone for 6 months then hMG added
hCG and hMG
Arm Description
Human Chorionic Gonadotropin 2000U~6000U, intramuscular injection, two times per week for 3 years.
Human Chorionic Gonadotropin 2000U~6000U, intramuscular injection, two times per week for six months, then 75~150IU human menopausal gonadotropin, intramuscular injection, two times per week, was added and last for the next 30 months.
Human Chorionic Gonadotropin 2000U~6000U and 75~150IU human menopausal gonadotropin, intramuscular injection, two times per week for 3 years.
Outcomes
Primary Outcome Measures
Sperm density
Sperm density will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits.
Secondary Outcome Measures
Semen volume
Sperm volume will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits.
Sperm activity
Sperm activity will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits.
The time for sperm to appear during treatment
The time for the sperm firstly appeared in the semen will be recorded.
Serum testosterone levels
The serum testosterone levels will be tested in every visit.
Testicular volume
Testicular volume will be measured using a Prader orchidometer.
Penis length
Penis length will be measured from the pubic symphysis to glans using a vernier caliper.
Pubic hair
Pubic hair will be evaluated according to Tanner pubertal stages.
Genitalia
Genitalia will be evaluated according to Tanner pubertal stages.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03687606
Brief Title
Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
Acronym
IHH
Official Title
Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in the Treatment of Male Patients With Isolated Hypogonadotropic Hypogonadism: an Open, Randomized Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Recruiting
Study Start Date
October 18, 2018 (Actual)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tongji Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the efficacy and safety of long term use of hCG alone or hCG plus hMG in the treatment of male patients with isolated hypogonadotropic hypogonadism (IHH). One third of the participants will receive hCG treatment alone and the other third of the participants will receive hCG treatment alone for six months, then the hMG will be added. And the last third of the participants will receive hCG and hMG treatment since the beginning of the treatment.
Detailed Description
The efficacy of hCG alone or hCG plus hMG in the treatment of male IHH patients was reported in some studies. However, these studies were mostly non-randomized controlled studies with small size of samples and short follow-up time. There was also no reported study which aimed to compare the efficacy and safety of long term use of hCG or hCG plus hMG in the treatment of male patients with IHH. So the difference in the efficacy and safety between long term use of hCG alone and hCG plus hMG in the treatment of IHH is unknown. In different reported studies, the hCG plus hMG treatment had two regimens: using hCG alone for six month, then hMG was added and using hCG plus hMG since the beginning of the treatment. The difference in the efficacy and safety between the above two regimes is also unknown.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Isolated Hypogonadotropic Hypogonadism, Kallmann Syndrome, Infertility
Keywords
Gonadotropin treatment, human chorionic gonadotropin, human menopausal gonadotropin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
210 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Human Chorionic Gonadotropin alone
Arm Type
Active Comparator
Arm Description
Human Chorionic Gonadotropin 2000U~6000U, intramuscular injection, two times per week for 3 years.
Arm Title
hCG alone for 6 months then hMG added
Arm Type
Experimental
Arm Description
Human Chorionic Gonadotropin 2000U~6000U, intramuscular injection, two times per week for six months, then 75~150IU human menopausal gonadotropin, intramuscular injection, two times per week, was added and last for the next 30 months.
Arm Title
hCG and hMG
Arm Type
Experimental
Arm Description
Human Chorionic Gonadotropin 2000U~6000U and 75~150IU human menopausal gonadotropin, intramuscular injection, two times per week for 3 years.
Intervention Type
Drug
Intervention Name(s)
Human Chorionic Gonadotropin
Other Intervention Name(s)
hCG
Intervention Description
White freeze-dried cake or powder with specifications of 1000U, 2000U, 5000U.
Intervention Type
Drug
Intervention Name(s)
human menopausal gonadotropin
Other Intervention Name(s)
hMG
Intervention Description
White freeze-dried cake or powder with specification of 75IU.
Primary Outcome Measure Information:
Title
Sperm density
Description
Sperm density will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits.
Time Frame
6 months.
Secondary Outcome Measure Information:
Title
Semen volume
Description
Sperm volume will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits.
Time Frame
6 months.
Title
Sperm activity
Description
Sperm activity will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits.
Time Frame
6 months.
Title
The time for sperm to appear during treatment
Description
The time for the sperm firstly appeared in the semen will be recorded.
Time Frame
6 months.
Title
Serum testosterone levels
Description
The serum testosterone levels will be tested in every visit.
Time Frame
3 months.
Title
Testicular volume
Description
Testicular volume will be measured using a Prader orchidometer.
Time Frame
3 months.
Title
Penis length
Description
Penis length will be measured from the pubic symphysis to glans using a vernier caliper.
Time Frame
3 months.
Title
Pubic hair
Description
Pubic hair will be evaluated according to Tanner pubertal stages.
Time Frame
3 months.
Title
Genitalia
Description
Genitalia will be evaluated according to Tanner pubertal stages.
Time Frame
3 months.
Other Pre-specified Outcome Measures:
Title
Height
Description
Height will be measured at every visit.
Time Frame
3 months.
Title
Weight
Description
Weight will be measured at every visit.
Time Frame
3 months.
Title
Feeling of inferiority scale score
Description
Feeling of inferiority scale scores will be obtained using feeling of inferiority scale.
Time Frame
3 months.
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18, ≤ 45 years old;
Adolescent dysplasia or loss of puberty: Genital Tanner score ﹤ 5, pubic hair Tanner score ﹤ 5;
Serum FSH and LH levels are low or in normal low value, testosterone was lower than normal range (1.75ng / ml, the lower limit of the normal blood testosterone reference range of Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology);
With or without olfactory loss/reduction;
Other pituitary hormone levels are normal;
Head MRI examination is normal;
Fertility is desired currently or will be desired in the future;
Understand and sign the informed consent form.
Exclusion Criteria:
Primary hypogonadism;
Acquired hypogonadotrophic hypogonadism;
A history of treatment with pulsed GnRH, hCG and FSH related hormones;
Receive testosterone replacement therapy for more than 6 months;
History of cryptorchidism or cryptorchidism;
The sperm density before treatment ≥1×10^6/ml;
Moderate or severe liver and kidney dysfunction (ALT>120IU/L, AST>80IU/L, CR>115μmol/L);
The karyotype is 45,X or 47,XXY and 48, XXXY and other abnormal karyotypes;
True hermaphroditism and pseudohermaphroditism;
Sex hormone abnormalities caused by adrenal lesions;
Hypogonadism secondary to other systemic diseases;
Abnormal secretion of hormones caused by brain lesions (such as pituitary tumors);
There are other hormone abnormalities in the pituitary;
There are contraindications for the treatment with hCG or hMG.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hao Xu, M.D
Phone
+86-15872427301
Email
haoxutjmu@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yinwei Chen, M.D
Phone
+86-15527953877
Email
913904361@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jihong Liu, M.D
Organizational Affiliation
Departments of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hao Xu, M.D
Phone
+86-15872427301
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data for all primary and secondary outcome measure will be available.
IPD Sharing Time Frame
Data will be available with 6 months of study completion.
IPD Sharing Access Criteria
Data access requests will be reviewed by the external independent review panel and Tongji hospital. Requester will be reqiured to sign a Data Acces Agreement.
Citations:
PubMed Identifier
22763096
Citation
Zacharin M, Sabin MA, Nair VV, Dabadghao P. Addition of recombinant follicle-stimulating hormone to human chorionic gonadotropin treatment in adolescents and young adults with hypogonadotropic hypogonadism promotes normal testicular growth and may promote early spermatogenesis. Fertil Steril. 2012 Oct;98(4):836-42. doi: 10.1016/j.fertnstert.2012.06.022. Epub 2012 Jul 3. Erratum In: Fertil Steril. 2013 May;99(6):1798. Dagabdhao, Preeti [corrected to Dabadghao, Preeti].
Results Reference
background
PubMed Identifier
18930190
Citation
Matsumoto AM, Snyder PJ, Bhasin S, Martin K, Weber T, Winters S, Spratt D, Brentzel J, O'Dea L. Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa; GONAL-f): long-term treatment in azoospermic men with hypogonadotropic hypogonadism. Fertil Steril. 2009 Sep;92(3):979-990. doi: 10.1016/j.fertnstert.2008.07.1742. Epub 2008 Oct 18.
Results Reference
background
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Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
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