Klinefelter Syndrome
Conditions
Keywords
Metabolic syndrome, Infertility, Aromatase, Testosterone/estradiol ratio, mTESE biopsy, GLP1 agonists
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.
Interventions
DRUGAnastrozole
This will be an experimental treatment for 26 weeks in Group 1 Arm A and Arm B as well for Group 2 Arm D
DRUGSemaglutide
This will be an experimental treatment for 26 weeks in Group 2 Arm E
DRUGhuman chorionic gonadotropin
This will be an experimental treatment for 26 weeks in addition to anastrozole in Group 1 - Arm B
DRUGTestosterone gel
This will be an active comparator for 26 weeks in Group 2 - Arm C
Sponsors
Georgios Papadakis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Two designs according to the presence of fertility desire (Design 1) or high metabolic risk (Design 2)
Eligibility
Sex/Gender
MALE
Age
16 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Switzerland
Contacts
CONTACTGEORGIOS PAPADAKIS, MD
CONTACTRIKIATOU FRANCIOLI, MD
PRINCIPAL_INVESTIGATORGEORGIOS PAPADAKIS, MD
Service of endocrinology, diabetes & metabolism, CHUV, Lausanne University Hospital
Outcome results
None listed