Clinical trial NCT05586802: Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome
Official title: Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Klinefelter Syndrome
Keywords: Metabolic syndrome
Infertility
Aromatase
Testosterone/estradiol ratio
mTESE biopsy
GLP1 agonists
Lead sponsor: University of Lausanne Hospitals
Sponsor class: OTHER
First posted: 2022-10-19
Enrollment: 150
Sex: MALE
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two designs according to the presence of fertility desire (Design 1) or high metabolic risk (Design 2)
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Design 1 : sperm retrieval rate at mTESE biopsy
timeFrame: mTESE biopsy 26 weeks after hormonal intervention
measure: Design 2 : change in insulin resistance index (HOMA-IR)
timeFrame: From baseline to week 26 of intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Service of Endocrinology, Diabetes & Metabolism
Study officials:
affiliation: Service of endocrinology, diabetes & metabolism, CHUV, Lausanne University Hospital
name: GEORGIOS PAPADAKIS, MD
role: PRINCIPAL_INVESTIGATOR
References: