Clinical trial NCT06294990: Klinefelter Syndrome and Testosterone Treatment in Puberty
Official title: Klinefelter Syndrome - the Effect of Testosterone Treatment in Puberty. a Randomized, Double-blind Placebo-controlled Intervention Study: 'The TiPY Study'
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Klinefelter Syndrome
Keywords: Klinefelter syndrome
Puberty
Body composition
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2024-03-06
Enrollment: 32
Sex: MALE
Minimum age (years): 10
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, national, randomized, double-blind, placebo-controlled intervention study
Primary purpose: TREATMENT

Brief summary: The goal of this randomized clinical trial is to study the effect of testosterone replacement therapy during puberty in boys with Klinefelter syndrome (KS, 47,XXY).

The main questions to answer are how treatment with testosterone will affect body fat mass, lipid and glucose metabolism, growth and body proportions, bone mineralization as well as effects on neurocognitive development and emotional and social difficulties.

Participants will be randomized to two years treatment with testosterone or placebo.

Detailed description: Klinefelter syndrome (KS, 47,XXY) is the most frequent sex chromosome disorder with a prevalence of 1:660 boys. Patients with KS are hypogonadal due to a progressive testicular destruction starting already in childhood. Consequently, the adult male with KS is characterized by small testes, signs of incomplete virilization (e.g. lack of voice deepening, sparse face and body hair, gynecomastia, low muscle mass, reduced penile length), hypergonadotropic hypogonadism, infertility and increased risk of metabolic syndrome, diabetes, cardiovascular disease, osteoporosis and psychosocial and neurodevelopmental challenges. Adults with KS have a poor health and a prevention of the major co-morbidities associated with KS and thereby an improvement in the general health would have an enormous impact on the life of a large cohort of males worldwide.

Sufficient testosterone is not only important in the adult but also during puberty and adolescence for a normal virilization and to improve body composition and body proportions, as well as to maximize peak bone mass acquisition. It has therefore been internationally accepted and makes biological sense to consider testosterone replacement therapy (TRT) during puberty in KS. However, there are no evidence based recommendations, and during recent years TRT in puberty has been questioned and is no longer recommended in some countries. There is a need on an international level for evaluating the effect of this treatment. We therefore aim at evaluating the effect of 2 years TRT during early puberty in boys with KS aged 10 to 14 years in this national, multi-center, randomized, double-blind, placebo-controlled intervention study. The primary endpoint is to evaluate the effect on body fat mass. The secondary endpoints are to evaluate effects on lipid and glucose metabolism, growth and body proportions, bone mineralization as well as effects on neurocognitive development and emotional and social difficulties.

Eligibility criteria: Inclusion Criteria:

* 47,XXY Klinefelter syndrome
* Age 10-14 years at inclusion
* Luteinizing Hormone \> +2 standard deviations (SD) by ultrasensitive luteinizing hormone assay
* Free Testosterone\<+2 standard deviations
* Signed consent from parents

Exclusion Criteria:

* Previous or ongoing T treatment except for TRT because of micropenis
* Contraindications to testosterone treatment known hypersensitivity to testosterone or to any other constituent of the gel known or suspected prostatic cancer or breast carcinoma
* Participation in any other clinical trial

Primary outcomes:
measure: Changes in body fat mass
timeFrame: Baseline and 1 and two years
Secondary outcomes:
measure: Pubertal development and virilization
timeFrame: Every three months for two years
measure: Pubertal development and virilization
timeFrame: Every three months for two years
measure: Pubertal development and virilization
timeFrame: Every three months for two years
measure: Pubertal development and virilization
timeFrame: Every three months for two years
measure: Pubertal development and virilization
timeFrame: Every three months for two years
measure: Pubertal development and viriliztion
timeFrame: Every three months for two years
measure: Pubertal development and viriliztion
timeFrame: Every three months for two years
measure: Pubertal development and viriliztion
timeFrame: Every three months for two years
measure: Pubertal development and viriliztion
timeFrame: Every three months for two years
measure: Pubertal development and viriliztion
timeFrame: Every three months for two years
measure: Pubertal development and viriliztion
timeFrame: Every three months for two years
measure: Pubertal development
timeFrame: At base line, and at 1 and 2 years
measure: Anthropometry
timeFrame: Every three months for two years
measure: Anthropometry
timeFrame: Every three months for two years
measure: Anthropometry
timeFrame: Every three months for two years
measure: Anthropometry
timeFrame: At base line, and at 1 and 2 years
measure: Anthropometry
timeFrame: At base line, and at 1 and 2 years
measure: Bone health
timeFrame: At baseline and at 1 and two years
measure: Bone health
timeFrame: At base line, and at 1 and 2 years
measure: Measurement of bone turnover markers
timeFrame: At base line, and at 1 and 2 years
measure: Measurement of bone turnover markers
timeFrame: At base line, and at 1 and 2 years
measure: Measurement of bone turnover markers
timeFrame: At base line, and at 1 and 2 years
measure: Measurement of bone turnover markers
timeFrame: At base line, and at 1 and 2 years
measure: Measurement of bone turnover markers
timeFrame: At base line, and at 1 and 2 years
measure: Measurement of bone turnover markers
timeFrame: At base line, and at 1 and 2 years
measure: Measurement of bone turnover markers
timeFrame: At base line, and at 1 and 2 years
measure: Measurement of bone turnover markers
timeFrame: At base line, and at 1 and 2 years
measure: Changes in growth
timeFrame: Base line and at 1 and 2 years
measure: Measurement of serum concentrations of growth factors
timeFrame: At base line, and at 1 and 2 years
measure: Muscle strength
timeFrame: Every three months for two years
measure: Muscle strength
timeFrame: Every three months for two years
measure: Changes i QTc
timeFrame: Base line and at 1 and 2 years
measure: Changes in markers of lipids
timeFrame: Base line and at 1 and 2 years
measure: Changes in markers of metabolism
timeFrame: Base line and at 1 and 2 years
measure: Changes in markers of metabolism
timeFrame: Base line and at 1 and 2 years
measure: Changes in markers of metabolism
timeFrame: Base line and at 1 and 2 years
measure: Changes in markers of metabolism
timeFrame: Base line and at 1 and 2 years
measure: Changes in markers of metabolism
timeFrame: Base line and at 1 and 2 years
measure: Changes in markers of inflammation
timeFrame: Base line and at 1 and 2 years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Neuropsychological evaluation
timeFrame: Baseline and after two years
measure: Cryopreservation of spermatozoa
timeFrame: After 2 years
measure: Epigenetic
timeFrame: At base line, and at 1 and 2 years
measure: Genetic effects
timeFrame: At base line, and at 1 and 2 years
measure: Small non-coding RNA
timeFrame: At base line, and at 1 and 2 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital, Rigshospitalet
Study officials:
affiliation: Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
name: Lise Aksglaede, MD
role: PRINCIPAL_INVESTIGATOR
References: