Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Design 1 : sperm retrieval rate at mTESE biopsy
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Klinefelter syndrome (47,XXY or mosaicism)
- •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
- •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)
排除标准
- •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)
研究组 & 干预措施
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
干预措施: Anastrozole (Drug)
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
干预措施: Testosterone gel (Drug)
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
干预措施: Anastrozole (Drug)
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
干预措施: Anastrozole (Drug)
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
干预措施: human chorionic gonadotropin (Drug)
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
干预措施: Semaglutide (Drug)
结局指标
主要结局
Design 1 : sperm retrieval rate at mTESE biopsy
时间窗: 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)
时间窗: From baseline to week 26 of intervention
HOMA-IR calculated using fasting glucose and insulin levels
次要结局
未报告次要终点
研究者
Georgios Papadakis
Senior Lecturer (Privat docent & MERclin)
University of Lausanne Hospitals