Klinefelter Syndrome and Testosterone Treatment in Puberty (TiPY)

Lise Aksglæde

Status and phase: Enrolling; Phase 4

Conditions: Klinefelter Syndrome

Treatments: Other: Placebo; Drug: Testosterone gel

Study type: Interventional

Funder types: Other

Identifiers

NCT06294990

2023-505854-16-00

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 estimated patients

Sex: Male

Ages: 10 to 14 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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32 participants in 2 patient groups, including a placebo group

Testosterone

Active Comparator group

Description:

Testosterone gel applied to the skin

Treatment:

Drug: Testosterone gel

Placebo

Placebo Comparator group

Description:

Placebo gel applied to the skin

Treatment:

Other: Placebo