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

Phase 4

Completed

Conditions: Klinefelter Syndrome

Interventions: Drug: testosterone cypionate 200mg/ml

Registration Number: NCT02408445

Lead Sponsor: University of Colorado, Denver

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 20

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Testosterone treatment	testosterone cypionate 200mg/ml	Testosterone cypionate (200 mg/ml) intramuscular injection

Primary Outcome Measures

Name	Time	Method
Change in Body Fat Percent Z-score	Baseline and 3 months	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.

Secondary Outcome Measures

Name	Time	Method
Serum Luteinizing Hormone (LH)	baseline only	Serum will be collected at the first study visit prior to randomization. Ultrasensitive LH will be measured.
Change in Raw Score on the Alberta Infant Motor Scale	3 months	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.
Change in Total Motor Standard Score on the Peabody Developmental Motor Scales 2	3 months	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.
Serum Follicle Stimulating Hormone (FSH)	baseline only	Serum will be collected at the first study visit prior to randomization. Ultrasensitive FSH will be measured.
Serum Total Testosterone	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)	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)	baseline only	Serum will be collected at the first study visit prior to randomization. AMH levels will be measured.
Leptin	baseline only	Serum will be collected at the first study visit prior to randomization. Leptin levels will be measured.
Change in Penile Length	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 Score on the Movement Assessment of Infants (MAI)	3 months	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.
Change in Fat Free Mass	Baseline and 3 months	Fat free mass (lean mass) will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period.