Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome

Klinefelter Syndrome Clinical Trial

— KLIN-HEALTH  

Official title:

Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05586802
• Other study ID #: PZ00P3_202151
• Status: Recruiting
• Phase: Phase 3
• Start date: March 21, 2023
• Est. completion date: April 1, 2026

Study information

• Verified date: December 2023
• Source: University of Lausanne Hospitals
• Contact: GEORGIOS PAPADAKIS, MD
• Phone: +41795560308
• Email: georgios.papadakis[@]chuv.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study seeks primarily to determine whether modulation of systemic and testicular sex steroids balance by aromatase inhibitors will positively affect the metabolic health and spermatogenesis of men with Klinefelter syndrome (KFS) as compared to the current state of the art for each issue. Secondary objectives of this study are (i) to unravel the heterogeneity of the reproductive and metabolic phenotype of men with KFS by performing a multi-omic analysis in a large cohort at baseline; (ii) to evaluate the efficacy of semaglutide-induced weight loss to achieve metabolic and reproductive benefit in men with Klinefelter syndrome as compared to standard testosterone replacement; (ii) to assess whether addition of hCG to aromatase inhibitors further increases intratesticular testosterone and promotes spermatogenesis in men with KFS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: April 1, 2026
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years to 65 Years

Eligibility

Inclusion Criteria:

-Diagnosis of Klinefelter syndrome (47,XXY or mosaicism)

Design 1:

• Age range: 16-40 years old
• Intention to become parent or interest in fertility preservation
• Confirmed azoospermia (lack of spermatozoids) after centrifugation of one semen sample

Design 2:

• Age range: 18-65 years old
• No interest in fertility or fertility preservation
• Hypogonadism at diagnosis or after wash-out of testosterone replacement therapy
• High metabolic risk defined as overweight (BMI 25-28 kg/m2) and insulin resistance (HOMA-IR > 2.6)

Exclusion Criteria:

• Contraindications to testosterone-rising therapies (prostate or breast cancer, PSA > 4 µg/l, active liver disease, symptomatic heart disease)
• Decreased life expectancy due to terminal disease
• Known or suspected non-compliance, drug or alcohol abuse
• Inability to follow the procedures of the study (language problems, severe psychological or mental disorders)

Related Conditions & MeSH terms

• Klinefelter Syndrome
• Syndrome

Intervention

Drug:
• Anastrozole
This will be an experimental treatment for 26 weeks in Group 1 Arm A and Arm B as well for Group 2 Arm D
• Semaglutide
This will be an experimental treatment for 26 weeks in Group 2 Arm E
• human chorionic gonadotropin
This will be an experimental treatment for 26 weeks in addition to anastrozole in Group 1 - Arm B
• Testosterone gel
This will be an active comparator for 26 weeks in Group 2 - Arm C

Locations

Country	Name	City	State
Switzerland	Service of Endocrinology, Diabetes & Metabolism	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
Georgios Papadakis

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Design 1 : sperm retrieval rate at mTESE biopsy	Sperm retrieval rate at mTESE biopsy (Group A and B)	mTESE biopsy 26 weeks after hormonal intervention
Primary	Design 2 : change in insulin resistance index (HOMA-IR)	HOMA-IR calculated using fasting glucose and insulin levels	From baseline to week 26 of intervention