Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)

Phase 4

Recruiting

• Conditions: Isolated Hypogonadotropic Hypogonadism; Kallmann Syndrome; Infertility
• Interventions: Drug: Human Chorionic Gonadotropin; Drug: human menopausal gonadotropin

• Registration Number: NCT03687606
• Lead Sponsor: Tongji Hospital

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.

Study Timeline

• Study First Submitted: 2018-09-16
• Study First Submitted QC: 2018-09-26
• Study First Posted: 2018-09-27
• Study Start: 2018-10-18
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-07
• Last Update Posted: 2020-04-08
• Primary Completion: 2024-10-01
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 210

Inclusion Criteria

1. Age ≥ 18, ≤ 45 years old;
2. Adolescent dysplasia or loss of puberty: Genital Tanner score ﹤ 5, pubic hair Tanner score ﹤ 5;
3. 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);
4. With or without olfactory loss/reduction;
5. Other pituitary hormone levels are normal;
6. Head MRI examination is normal;
7. Fertility is desired currently or will be desired in the future;
8. Understand and sign the informed consent form.

Exclusion Criteria

1. Primary hypogonadism;
2. Acquired hypogonadotrophic hypogonadism;
3. A history of treatment with pulsed GnRH, hCG and FSH related hormones;
4. Receive testosterone replacement therapy for more than 6 months;
5. History of cryptorchidism or cryptorchidism;
6. The sperm density before treatment ≥1×10^6/ml;
7. Moderate or severe liver and kidney dysfunction (ALT>120IU/L, AST>80IU/L, CR>115μmol/L);
8. The karyotype is 45,X or 47,XXY and 48, XXXY and other abnormal karyotypes;
9. True hermaphroditism and pseudohermaphroditism;
10. Sex hormone abnormalities caused by adrenal lesions;
11. Hypogonadism secondary to other systemic diseases;
12. Abnormal secretion of hormones caused by brain lesions (such as pituitary tumors);
13. There are other hormone abnormalities in the pituitary;
14. There are contraindications for the treatment with hCG or hMG.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
hCG and hMG	Human Chorionic Gonadotropin	Human Chorionic Gonadotropin 2000U\~6000U and 75\~150IU human menopausal gonadotropin, intramuscular injection, two times per week for 3 years.
Human Chorionic Gonadotropin alone	Human Chorionic Gonadotropin	Human Chorionic Gonadotropin 2000U\~6000U, intramuscular injection, two times per week for 3 years.
hCG alone for 6 months then hMG added	Human Chorionic Gonadotropin	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.
hCG alone for 6 months then hMG added	human menopausal gonadotropin	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.
hCG and hMG	human menopausal gonadotropin	Human Chorionic Gonadotropin 2000U\~6000U and 75\~150IU human menopausal gonadotropin, intramuscular injection, two times per week for 3 years.

Primary Outcome Measures

Name	Time	Method
Sperm density	6 months.	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

Name	Time	Method
Serum testosterone levels	3 months.	The serum testosterone levels will be tested in every visit.
The time for sperm to appear during treatment	6 months.	The time for the sperm firstly appeared in the semen will be recorded.
Pubic hair	3 months.	Pubic hair will be evaluated according to Tanner pubertal stages.
Semen volume	6 months.	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	6 months.	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.
Testicular volume	3 months.	Testicular volume will be measured using a Prader orchidometer.
Penis length	3 months.	Penis length will be measured from the pubic symphysis to glans using a vernier caliper.
Genitalia	3 months.	Genitalia will be evaluated according to Tanner pubertal stages.

Trial Locations

Locations (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China