Body Composition in Infants With Klinefelter Syndrome and Effects of Testosterone Treatment

Study Overview
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Brief Summary
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This research study in infant males with Klinefelter syndrome (47,XXY) will learn more about body composition (muscle and fat) and male hormones and look at the effect of testosterone shots on body composition. The Investigators know that older boys and men with Klinefelter syndrome often have more fat compared to muscle than adults without Klinefelter syndrome, but we do not know if this difference is present at birth or develops over time. The Investigators will learn if body composition and motor skills are improved with testosterone treatment in infants with Klinefelter syndrome.

Official Title
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Body Composition in Infants With Klinefelter Syndrome and Effects of Testosterone Treatment

Conditions
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Klinefelter Syndrome

Intervention / Treatment
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* Drug: testosterone cypionate 200mg/ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male infants with 47,XXY karyotype Exclusion Criteria: Gestational age at birth <36 weeks Birth weight <5%ile or >95% for gestational age History of thrombosis in a first degree relative Exposure to androgen therapy outside of the study protocol.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 108 Days

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Testosterone treatment<br>Testosterone cypionate (200 mg/ml) intramuscular injection | Drug: testosterone cypionate 200mg/ml<br>* Subjects in this group will be randomized to receive testosterone cypionate 200 mg/ml to be given intramuscularly every 4 weeks for a total of 3 doses.<br>|
| No Intervention: No treatment<br>Subjects will not receive any testosterone during the study period. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Fat Percent Z-score | Body fat percentage will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period. Age and sex-normed z-scores will be calculated. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Change in the z-score over time, if following a normal growth curve, is 0. Positive change in z-scores indicates a gain in body fat above growth typically expected. Negative change in z-scores indicates a gain in body fat that is less than typically expected. | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Luteinizing Hormone (LH) | Serum will be collected at the first study visit prior to randomization. Ultrasensitive LH will be measured. | baseline only | 
| Serum Follicle Stimulating Hormone (FSH) | Serum will be collected at the first study visit prior to randomization. Ultrasensitive FSH will be measured. | baseline only | 
| Serum Total Testosterone | Serum will be collected at the first study visit prior to randomization. Total testosterone by mass spectroscopy will be measured. | baseline only | 
| Serum Inhibin B (INHB) | Serum will be collected at the first study visit prior to randomization. Inhibin B levels will be measured. | baseline only | 
| Serum Anti-Mullerian Hormone (AMH) | Serum will be collected at the first study visit prior to randomization. AMH levels will be measured. | baseline only | 
| Leptin | Serum will be collected at the first study visit prior to randomization. Leptin levels will be measured. | baseline only | 
| Change in Raw Score on the Alberta Infant Motor Scale | Muscle tone and motor development will be assessed by an occupational therapist using the standardized Alberta Infant Motor Scale (AIMS). The AIMS scale measures infant motor maturation from birth until the age of independent walking. An occupational therapists assesses 58 motor behavior items in 4 position categories: prone (21 items), supine (9 items), sitting (12 items) & standing(16 standing). Each item receives one point (range of raw scores 0-58), with higher scores indicating more skills acquired. For change in scores, the raw score at 3 months was subtracted from the baseline raw score. | 3 months | 
| Change in Score on the Movement Assessment of Infants (MAI) | Muscle tone and motor development will be assessed by an occupational therapist using the standardized Movement Assessment of Infants (MAI). The MAI evaluates four domains: muscle tone, primitive reflex, automatic reactions and volitional movement. All items are scored 1-5 and summed to generate a Total Risk Score. Lower scores indicate better function, and Total Risk Scores of 8 or more indicate high risk. | 3 months | 
| Change in Total Motor Standard Score on the Peabody Developmental Motor Scales 2 | Motor development will be assessed by an occupational therapist using the standardized Peabody Developmental Motor Scales 2. Standard scores are normalized to age with a mean of 100 and standard deviation of 15. Change in standard score was calculated as the differences between the subject's standard score at 3 months minus the standard score at baseline. A positive change in standard scores would indicate greater growth on the measure relative to peers, while a negative number would indicate slower growth on the measure relative to peers. | 3 months | 
| Change in Penile Length | Stretched penile length will be measured by a physician before randomization and at the end of the study period. | Baseline and 3 months | 
| Change in Fat Free Mass | Fat free mass (lean mass) will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period. | Baseline and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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body composition, Klinefelter syndrome, XXY, sex chromosome variation, sex chromsome aneuploidy