Klinefelter Syndrome
Conditions
Keywords
body composition, Klinefelter syndrome, XXY, sex chromosome variation, sex chromsome aneuploidy
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.
Interventions
DRUGtestosterone cypionate 200mg/ml
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.
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
42 Days to 108 Days
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 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. |
| 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 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Treatment Testosterone cypionate (200 mg/ml) intramuscular injection
testosterone cypionate 200mg/ml: 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. | 10 |
| No Treatment Subjects will not receive any testosterone during the study period. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Testosterone Treatment | Total | No Treatment |
|---|---|---|---|
| Age, Continuous | 73 days STANDARD_DEVIATION 22 | 72 days STANDARD_DEVIATION 22 | 70 days STANDARD_DEVIATION 23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 20 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 17 Participants | 9 Participants |
| Region of Enrollment United States | 10 participants | 20 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 20 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 5 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
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.
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Change in Body Fat Percent Z-score | -0.12 score on a scale | Standard Deviation 0.65 |
| No Treatment | Change in Body Fat Percent Z-score | 0.92 score on a scale | Standard Deviation 0.62 |
Secondary
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.
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Change in Fat Free Mass | 1.4 kg | Standard Deviation 0.4 |
| No Treatment | Change in Fat Free Mass | 0.6 kg | Standard Deviation 0.3 |
Secondary
Change in Penile Length
Stretched penile length will be measured by a physician before randomization and at the end of the study period.
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Change in Penile Length | 0.9 cm | Standard Deviation 0.5 |
| No Treatment | Change in Penile Length | -0.3 cm | Standard Deviation 0.6 |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Change in Raw Score on the Alberta Infant Motor Scale | 10.5 raw score | Standard Deviation 4.9 |
| No Treatment | Change in Raw Score on the Alberta Infant Motor Scale | 8.9 raw score | Standard Deviation 7.1 |
Secondary
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.
Time frame: 3 months
Population: Data for this measurement was not collected for any of the participants.
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Change in Total Motor Standard Score on the Peabody Developmental Motor Scales 2 | 2.8 change in standard score | Standard Deviation 7.3 |
| No Treatment | Change in Total Motor Standard Score on the Peabody Developmental Motor Scales 2 | 2.0 change in standard score | Standard Deviation 6.9 |
Secondary
Leptin
Serum will be collected at the first study visit prior to randomization. Leptin levels will be measured.
Time frame: baseline only
Population: Unable to be analyzed due to insufficient quantities of serum collected. Prioritized hormone assays first.
Secondary
Serum Anti-Mullerian Hormone (AMH)
Serum will be collected at the first study visit prior to randomization. AMH levels will be measured.
Time frame: baseline only
Population: Analysis was completed only on subjects for which sufficient blood was able to be obtained and that has been measured at this time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Serum Anti-Mullerian Hormone (AMH) | 1377 pmol/l | Standard Deviation 688 |
| No Treatment | Serum Anti-Mullerian Hormone (AMH) | 2208 pmol/l | Standard Deviation 862 |
Secondary
Serum Follicle Stimulating Hormone (FSH)
Serum will be collected at the first study visit prior to randomization. Ultrasensitive FSH will be measured.
Time frame: baseline only
Population: Analysis was completed only on subjects for which sufficient blood was able to be obtained and that has been measured at this time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Serum Follicle Stimulating Hormone (FSH) | 1.8 mIU/mL | Standard Deviation 0.3 |
| No Treatment | Serum Follicle Stimulating Hormone (FSH) | 1.7 mIU/mL | Standard Deviation 0.5 |
Secondary
Serum Inhibin B (INHB)
Serum will be collected at the first study visit prior to randomization. Inhibin B levels will be measured.
Time frame: baseline only
Population: Analysis was completed only on subjects for which sufficient blood was able to be obtained and that has been measured at this time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Serum Inhibin B (INHB) | 244 pg/ml | Standard Deviation 96 |
| No Treatment | Serum Inhibin B (INHB) | 355 pg/ml | Standard Deviation 151 |
Secondary
Serum Luteinizing Hormone (LH)
Serum will be collected at the first study visit prior to randomization. Ultrasensitive LH will be measured.
Time frame: baseline only
Population: Analysis was completed only on subjects for which sufficient blood was able to be obtained and that has been measured at this time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Serum Luteinizing Hormone (LH) | 2.5 mIU/mL | Standard Deviation 1.1 |
| No Treatment | Serum Luteinizing Hormone (LH) | 2.5 mIU/mL | Standard Deviation 1.3 |
Secondary
Serum Total Testosterone
Serum will be collected at the first study visit prior to randomization. Total testosterone by mass spectroscopy will be measured.
Time frame: baseline only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Treatment | Serum Total Testosterone | 181 ng/dl | Standard Deviation 100 |
| No Treatment | Serum Total Testosterone | 166 ng/dl | Standard Deviation 30 |