Clinical trial NCT03325647: TESTO: Testosterone Effects on Short-Term Outcomes in Infants With XXY
Official title: TESTO: Testosterone Effects on Short-Term Outcomes in Infants With XXY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Klinefelter Syndrome
Keywords: body composition
klinefelter syndrome
XXY
sex chromosome variation
sex chromosome aneuploidy
testosterone
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2017-10-30
Enrollment: 72
Sex: MALE
Minimum age (years): 31
Maximum age (years): 90
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This research study in infant males with Klinefelter syndrome (47,XXY) will learn more about the effect of testosterone on early health and development. The study is a total of three visits over 6 months with assessments of motor skills, body composition (muscle and fat), and hormone levels. This is a randomized, placebo-controlled study but all infants will receive testosterone treatment during the study period. The investigators will learn how testosterone treatment in infancy effects short term outcome measures on health and development.

Detailed description: XXY (also known as Klinefelter syndrome) is the most common chromosomal abnormality in males, affecting 1/600 boys. The extra X chromosome leads to insufficient development of the testicles and subsequent testosterone deficiency. Males with XXY also have a high risk for developmental delays, learning disabilities, and cardiovascular disease. An essential question is how much of this risk is because of testosterone deficiency and could therefore be reduced by testosterone supplementation, particularly during critical periods of development.

In typical male development, there is a surge of testosterone in the first few months of life, commonly known as the "mini-puberty period of infancy." This testosterone surge may be critical for neurodevelopmental and cardiometabolic programming throughout life. Recently there has been increased off-label use of testosterone in infants with XXY, however neither the short or long term safety or efficacy have been evaluated. This study aims to quantify the short term effects of testosterone treatment in infants with XXY on neurodevelopment, growth, body composition, testicular function, and safety parameters. This is a double blind randomized placebo controlled trial of testosterone injections 25 mg every 4 weeks for 3 doses in boys with XXY enrolled between 1 and 3 months of age. Outcomes including body fat percentage, scaled motor developmental scores, growth velocity, testicular hormone concentrations, specific metabolites, and safety parameters will be assessed 12 weeks into the study. The groups will then cross-over (all subjects will receive testosterone during the study period) and the outcomes will be reassessed 24 weeks into the study. The secondary questions the investigators will answer with this cross-over is 1) whether benefits in the treatment group at 12 weeks are sustained at 24 weeks, and 2) whether the same benefits are seen if treated after the mini-puberty period.

Eligibility criteria: Inclusion Criteria:

* Male infants with 47,XXY karyotype identified prenatally who are 4-12 weeks old (31 to 90 days of age). 47,XXY must be from a diagnostic test such as Chorionic Villus Sampling (CVS), amniocentesis, or post-natal blood/tissue. Non-invasive prenatal screening results alone will not be accepted.

Exclusion Criteria:

* \>20 percent mosaicism for a normal cell line
* Gestational age at birth \<36 weeks
* Birth weight \<2.5th percentile or \>97.5 percentile for age (small or large for gestational age)
* History of thrombosis in self or a first degree relative
* Exposure to androgen therapy outside the study protocol
* Use of medications known to affect body composition, such as growth hormone or insulin
* Known allergy to the testosterone cypionate solution components including benzyl benzoate, benzyl alcohol, or cottonseed oil

Primary outcomes:
measure: Change in Body Fat Percentage
timeFrame: Baseline and 3 months
measure: Change in Composite Motor Score on Alberta Infant Motor Scale
timeFrame: 3 months
measure: Change in C14:1 Long Chain Acylcarnitines (LCAC) through targeted metabolomics
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Change in height
timeFrame: 6 months
measure: Change in weight
timeFrame: 6 months
measure: Change in weight-for-length
timeFrame: 6 months
measure: Change in waist circumference
timeFrame: 6 months
measure: Change in serum leptin
timeFrame: 6 months
measure: Change in lipids
timeFrame: 6 months
measure: Change in insulin
timeFrame: 6 months
measure: Change in serum Luteinizing Hormone (LH)
timeFrame: 6 months
measure: Change in serum Follicle Stimulating Hormone (FSH)
timeFrame: 6 months
measure: Change in Inhibin B (INHB)
timeFrame: 6 months
measure: Change in Anti-Mullerian Hormone (AMH)
timeFrame: 6 months
measure: Change in Total Testosterone (Total T)
timeFrame: 6 months
measure: Change in Gross Motor Scores on the Peabody Developmental Motor Scales 2
timeFrame: 6 months
measure: Change in Gross Motor Scores on the Alberta Infant Motor Scales
timeFrame: 6 months
measure: Change in Fine Motor Scores
timeFrame: 6 months
measure: Change in Cognitive and Language Composite Scores on the Bayley III
timeFrame: 6 months
measure: Change in Adaptive Functioning
timeFrame: 6 months
measure: Change in Number and Type of Adverse Events
timeFrame: 6 months
measure: Change in Serum BCAA, other LCAC
timeFrame: 6 months
measure: Change in Pathway analysis
timeFrame: 3 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Shanlee M Davis, MD
role: PRINCIPAL_INVESTIGATOR
References: