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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Infertility; Kallmann Syndrome; Isolated Hypogonadotropic Hypogonadism
• Intervention / Treatment: Drug: Human Chorionic Gonadotropin; Drug: human menopausal gonadotropin

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 Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hao Xu, M.D; Phone Number: +86-15872427301; Email: haoxutjmu@163.com
• Study Contact Backup: Name: Yinwei Chen, M.D; Phone Number: +86-15527953877; Email: 913904361@qq.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Hao Xu, M.D; Phone Number: +86-15872427301

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Human Chorionic Gonadotropin alone; Human Chorionic Gonadotropin 2000U~6000U, intramuscular injection, two times per week for 3 years.	Drug: Human Chorionic Gonadotropin; White freeze-dried cake or powder with specifications of 1000U, 2000U, 5000U.; Other Names: hCG
Experimental: hCG alone for 6 months then hMG added; 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.	Drug: Human Chorionic Gonadotropin; White freeze-dried cake or powder with specifications of 1000U, 2000U, 5000U.; Other Names: hCG; Drug: human menopausal gonadotropin; White freeze-dried cake or powder with specification of 75IU.; Other Names: hMG
Experimental: hCG and hMG; Human Chorionic Gonadotropin 2000U~6000U and 75~150IU human menopausal gonadotropin, intramuscular injection, two times per week for 3 years.	Drug: Human Chorionic Gonadotropin; White freeze-dried cake or powder with specifications of 1000U, 2000U, 5000U.; Other Names: hCG; Drug: human menopausal gonadotropin; White freeze-dried cake or powder with specification of 75IU.; Other Names: hMG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months.

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height	Height will be measured at every visit.	3 months.
Weight	Weight will be measured at every visit.	3 months.
Feeling of inferiority scale score	Feeling of inferiority scale scores will be obtained using feeling of inferiority scale.	3 months.

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Investigators: Principal Investigator: Jihong Liu, M.D, Departments of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Publications and helpful links

General Publications

• 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].
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2018
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: September 16, 2018
• First Submitted That Met QC Criteria: September 26, 2018
• First Posted (Actual): September 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2020
• Last Update Submitted That Met QC Criteria: April 7, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: human chorionic gonadotropin; human menopausal gonadotropin; Gonadotropin treatment
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Disorder of Sex Development, 46,XY; Infertility; Kallmann Syndrome; Hypogonadism; Physiological Effects of Drugs; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Chorionic Gonadotropin; Menotropins
• Other Study ID Numbers: TJ-IRB20180906

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No