Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome
- Conditions
- Klinefelter Syndrome
- Interventions
- Registration Number
- NCT05586802
- Lead Sponsor
- Georgios Papadakis
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 150
-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)
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2 (Metabolic Risk) - randomized to Arm C Testosterone gel Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an active comparator by a testosterone gel Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm A Anastrozole Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have negative sperm retrieval (no detectable spermatozoids), subsequently randomized to receive an hormonal stimulation for 26 weeks Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B Anastrozole Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have negative sperm retrieval (no detectable spermatozoids), subsequently randomized to receive an hormonal stimulation for 26 weeks Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B human chorionic gonadotropin Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have negative sperm retrieval (no detectable spermatozoids), subsequently randomized to receive an hormonal stimulation for 26 weeks Group 2 (Metabolic Risk) - randomized to Arm D Anastrozole Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an an experimental treatment Group 2 (Metabolic Risk) - randomized to Arm E Semaglutide Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an an experimental treatment
- Primary Outcome Measures
Name Time Method Design 1 : sperm retrieval rate at mTESE biopsy mTESE biopsy 26 weeks after hormonal intervention Sperm retrieval rate at mTESE biopsy (Group A and B)
Design 2 : change in insulin resistance index (HOMA-IR) From baseline to week 26 of intervention HOMA-IR calculated using fasting glucose and insulin levels
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Service of Endocrinology, Diabetes & Metabolism
🇨🇭Lausanne, Switzerland