Klinefelter Syndrome and Testosterone Treatment in Puberty

NCT ID: NCT06294990

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-15
• Study Completion Date: 2029-12-31

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.

Conditions

Klinefelter Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Testosterone

Testosterone gel applied to the skin

Group Type: ACTIVE_COMPARATOR

Testosterone gel

Intervention Type: DRUG

Two years treatment with testosterone

Placebo

Placebo gel applied to the skin

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Two years treatment with placebo

Interventions

Testosterone gel

Two years treatment with testosterone

Intervention Type: DRUG

Placebo

Two years treatment with placebo

Intervention Type: OTHER

Other Intervention Names

Testosterone; Testosterone

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Lise Aksglæde

OTHER

Sponsor Role: lead

Responsible Party

Lise Aksglæde

Principal investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lise Aksglaede, MD

Role: PRINCIPAL_INVESTIGATOR

Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Locations

Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Lise Aksglaede, MD

Role: CONTACT

lise.aksglaede@regionh.dk

+45 35455064

Facility Contacts

Lise Aksglaede, MD

Role: primary

lise.aksglaede@regionh.dk

+45353550564

References

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-2024-095628.

Reference Type: DERIVED

PMID: 40090688 (View on PubMed)

Other Identifiers

2023-505854-16-00

Identifier Type: -

Identifier Source: org_study_id