Klinefelter Syndrome and Testosterone Treatment in Puberty
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Testosterone gel, Placebo.
- Who it may be relevant to
- Registry conditions: Klinefelter Syndrome. Basic parameters: 10 years — 14 years · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Denmark
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Klinefelter Syndrome - the Effect of Testosterone Treatment in Puberty. a Randomized, Double-blind Placebo-controlled Intervention Study: 'The TiPY Study'
Overview
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.
Interventions
- Drug Testosterone gel
Two years treatment with testosterone - Other Placebo
Two years treatment with placebo
Primary outcome measures
- Changes in body fat mass [Time frame: Baseline and 1 and two years]
Secondary outcome measures (12)
- Pubertal development and virilization [Time frame: Every three months for two years]
- Pubertal development and virilization [Time frame: Every three months for two years]
- Pubertal development and virilization [Time frame: Every three months for two years]
- Pubertal development and virilization [Time frame: Every three months for two years]
- Pubertal development and virilization [Time frame: Every three months for two years]
- Pubertal development and viriliztion [Time frame: Every three months for two years]
- Pubertal development and viriliztion [Time frame: Every three months for two years]
- Pubertal development and viriliztion [Time frame: Every three months for two years]
- Pubertal development and viriliztion [Time frame: Every three months for two years]
- Pubertal development and viriliztion [Time frame: Every three months for two years]
- Pubertal development and viriliztion [Time frame: Every three months for two years]
- Pubertal development [Time frame: At base line, and at 1 and 2 years]
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Triple blind
- Primary purpose
- Treatment
Study locations
Denmark · 1 center
- Copenhagen University Hospital, Rigshospitalet — Copenhagen
Publications
- Caspersen ID, Fritzboger AFO, Petersen JH, Birkebaek N, Christensen AR, Schou AJ, Kristensen K, Ross JL, Davis S, Butler G, van Rijn S, Juul A, Aksglaede L. Effect of testosterone treatment during puberty in boys with Klinefelter syndrome (The TIPY Study): protocol for a nationwide randomised, double-blinded, placebo-controlled study. BMJ Open. 2025 Mar 15;15(3):e095628. doi: 10.1136/bmjopen-2024- PMID 40090688
Identifiers
NCT: NCT06294990 · 2023-505854-16-00