Klinefelter’s syndrome is a male sex chromosome disorder affecting 1 in 500 males across all ethnic groups. Men with Klinefelter’s syndrome possess an additional X chromosome, resulting in a 47,XXY genotype. The additional X chromosome comes from sporadic errors during sperm or egg formation.
Klinefelter syndrome (47,XXY) is the most common chromosomal abnormality in humans and occurs in approximately 1 in 650 males. Testosterone deficiency develops during adolescence in the majority of individuals with XXY. However, there are no previous studies that evaluate the psychological and motor effects of testosterone replacement therapy in adolescents with XXY.
The study researchers are interested in learning if testosterone therapy initiated in early puberty in XXY (KS) will lead to improvements in psychological and/or motor skills. They are also interested in learning if genetic variations of the androgen receptor gene or the parent-of-origin of the extra X chromosome influence the response to testosterone therapy.
Specific psychological factors to be studied include verbal and nonverbal cognitive skills, attention, executive function (organization, problem-solving skills, inhibition), anxiety, language, self-esteem, and other behavioral factors. Motor skills to be studied include gross and fine motor skills, motor coordination, and motor planning.
Participants in the study will be randomized to one of two treatment groups, receiving either testosterone gel or placebo, for 12 months. 60% of the study group will receive testosterone, and 40% will receive placebo.
The research participants, parents/caregivers, and the members of the study team will be blinded to the treatment group, and will not know whether they are receiving testosterone gel or placebo treatments.
The supervising endocrinologist for the study will not be blinded and will know which patients are in the testosterone and placebo groups. This will allow him to monitor results to determine if participants in the placebo group may develop a significant need for testosterone therapy during the study period. If this occurs, the patient will be switched to the testosterone group and will continue to be monitored in the study.
All participants will be evaluated at the beginning of the study and at 1, 3, 6, and 12 months. Travel costs are included. Evaluations will include a combination of psychological and motor skills testing, questionnaires completed by the parent/caregiver and study participant, physical examinations, and blood draws for safety monitoring and genetic studies.
Participation in the trial will last one year and includes 5 clinic visits to the eXtraordinarY Kids Clinic at Children's Hospital Colorado in Denver.
Secondary Outcome Measures : - Serum Luteinizing Hormone (LH) [ Time Frame: baseline only ]Serum will be collected at the first study visit prior to randomization. Ultrasensitive LH will be measured.
- Serum Follicle Stimulating Hormone (FSH) [ Time Frame: baseline only ]Serum will be collected at the first study visit prior to randomization. Ultrasensitive FSH will be measured.
- Serum Total Testosterone [ Time Frame: baseline only ]Serum will be collected at the first study visit prior to randomization. Total testosterone by mass spectroscopy will be measured.
- Serum Inhibin B (INHB) [ Time Frame: baseline only ]Serum will be collected at the first study visit prior to randomization. Inhibin B levels will be measured.
- Serum Anti-Mullerian Hormone (AMH) [ Time Frame: baseline only ]Serum will be collected at the first study visit prior to randomization. AMH levels will be measured.
- Leptin [ Time Frame: baseline only ]Serum will be collected at the first study visit prior to randomization. Leptin levels will be measured.
- Change in score on the Alberta Infant Motor Scale [ Time Frame: 3 months ]Muscle tone and motor development will be assessed by an occupational therapist using the standardized Alberta Infant Motor Scale.
- Change in score on the Movement Assessment of Infants (MAI). [ Time Frame: 3 months ]Muscle tone and motor development will be assessed by an occupational therapist using the standardized Movement Assessment of Infants (MAI).
- Change in score on the Peabody Developmental Motor Scales 2 [ Time Frame: 3 months ]Motor development will be assessed by an occupational therapist using the standardized Peabody Developmental Motor Scales 2.
- Change in Penile length [ Time Frame: Baseline and 3 months ]Stretched penile length will be measured by a physician before randomization and at the end of the study period.
- Change in Fat free mass [ Time Frame: Baseline and 3 months ]Fat free mass will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period.