Klinefelter Syndrome and Testosterone Treatment in Puberty

Klinefelter Syndrome Clinical Trial

— TiPY  

Official title:

Klinefelter Syndrome - the Effect of Testosterone Treatment In Puberty. A Randomized, Double-blind Placebo-controlled Intervention Study: 'The TiPY Study'

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06294990
• Other study ID #: 2023-505854-16-00
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: December 31, 2029

Study information

• Verified date: March 2024
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 32
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 10 Years to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• Klinefelter Syndrome
• Syndrome

Intervention

Drug:
• Testosterone gel
Two years treatment with testosterone

Other:
• Placebo
Two years treatment with placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Lise Aksglæde

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in body fat mass	Evaluation of body fat percentage by whole body dual energy x-ray absorptiometry (DEXA) scan	Baseline and 1 and two years
Secondary	Pubertal development and virilization	Tanner staging	Every three months for two years
Secondary	Height	Measurement of height (cm)	Every three months for two years
Secondary	Weight	Measurement of weight (kg)	Every three months for two years
Secondary	Bone mineralization	Evaluated by DEXA scan	Baseline and 1 and two years
Secondary	Neuropsychological evaluation	Wechsler Intelligence Scale for Children® Fifth Edition (WISC®-V)	Baseline and two years
Secondary	Neuropsychological evaluation,	The test of variables of attention (TOVA)	Baseline and two years