Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
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.
Eligibility
Participation Requirements
Sex: Male
Minimum Age: 16
Maximum Age: 65
Healthy Volunteers: f
View:
• 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)
Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have positive sperm retrieval (detectable spermatozoids)
Experimental: Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm A
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
Experimental: Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B
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
Active_comparator: Group 2 (Metabolic Risk) - randomized to Arm C
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
Experimental: Group 2 (Metabolic Risk) - randomized to Arm D
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
Experimental: Group 2 (Metabolic Risk) - randomized to Arm E
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