TESTO: Testosterone Effects on Short-Term Outcomes in Infants With XXY
Condition: Klinefelter Syndrome
MeSH terms: Klinefelter Syndrome
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution; Placebo injectable saline
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Intervention MeSH terms: Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Care Provider, Investigator)
Primary purpose: Treatment
Keywords: body composition; klinefelter syndrome; XXY; sex chromosome variation; sex chromosome aneuploidy; testosterone