TESTO: Testosterone Effects on Short-Term Outcomes in Infants With XXY

University of Colorado, Denver72 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Conditions

Klinefelter Syndrome

Interventions

Testosterone Cypionate 200 Milligram/Milliliter Injectable SolutionDRUG

Subjects in one arm will be randomized to receive testosterone cypionate 200 mg/ml intramuscularly every 4 weeks for a total of three doses after visit 1, and receive placebo injectable saline for the same duration starting at visit 2. Subjects in the other arm will be randomized to receive placebo injectable saline every 4 weeks for a total of 3 doses after visit 1, and testosterone cypionate 200 mg/ml intramuscularly for the same duration starting at visit 2.

Placebo injectable salineDRUG

Eligibility

Sex: MALEMin age: 31 DaysMax age: 90 Days

Medical Language ↔ Plain English

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

Locations (1)

Children's Hospital Colorado

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Change in Body Fat Percentage

Body fat percentage will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period

Time frame: Baseline and 3 months

Change in Composite Motor Score on Alberta Infant Motor Scale

Motor development will be assessed using the standardized Alberta Infant Motor Scale

Time frame: 3 months

Change in C14:1 Long Chain Acylcarnitines (LCAC) through targeted metabolomics

Plasma will be processed and stored until batch analysis using electrospray tandem mass spectroscopy per standard protocols to quantify acylcarnitines (short, medium, and long-chain) and Branched-Chain Amino Acids (BCAA--leucine/isoleucine and valine) at baseline and 12 weeks.

Time frame: Baseline and 3 months

Secondary Outcomes

Change in height

Physical exam measurements will be measured by a physician at each visit

Time frame: 6 months

Change in weight

Physical exam measurements will be measured by a physician at each visit

Time frame: 6 months

Change in weight-for-length

Physical exam measurements will be measured by a physician at each visit

Time frame: 6 months

Change in waist circumference

Physical exam measurements will be measured by a physician at each visit

Time frame: 6 months

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.