Trial Outcomes & Findings for Body Composition in Infants With Klinefelter Syndrome and Effects of Testosterone Treatment (NCT NCT02408445)

NCT ID: NCT02408445

Last Updated: 2020-04-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 20 participants
• Primary outcome timeframe: Baseline and 3 months
• Results posted on: 2020-04-15

Participant Flow

Participant milestones

Measure	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.	No Treatment Subjects will not receive any testosterone during the study period.
Overall Study STARTED	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Testosterone Treatment n=10 Participants 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.	No Treatment n=10 Participants Subjects will not receive any testosterone during the study period.	Total n=20 Participants Total of all reporting groups
Age, Continuous	73 days STANDARD_DEVIATION 22 • n=5 Participants	70 days STANDARD_DEVIATION 23 • n=7 Participants	72 days STANDARD_DEVIATION 22 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Testosterone Treatment n=10 Participants 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.	No Treatment n=10 Participants Subjects will not receive any testosterone during the study period.
Change in Body Fat Percent Z-score	-0.12 score on a scale Standard Deviation 0.65	0.92 score on a scale Standard Deviation 0.62

SECONDARY outcome

Timeframe: 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.

Serum will be collected at the first study visit prior to randomization. Ultrasensitive LH will be measured.

Outcome measures

Measure	Testosterone Treatment n=6 Participants 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.	No Treatment n=8 Participants Subjects will not receive any testosterone during the study period.
Serum Luteinizing Hormone (LH)	2.5 mIU/mL Standard Deviation 1.1	2.5 mIU/mL Standard Deviation 1.3

SECONDARY outcome

Timeframe: 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.

Serum will be collected at the first study visit prior to randomization. Ultrasensitive FSH will be measured.

Outcome measures

Measure	Testosterone Treatment n=6 Participants 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.	No Treatment n=8 Participants Subjects will not receive any testosterone during the study period.
Serum Follicle Stimulating Hormone (FSH)	1.8 mIU/mL Standard Deviation 0.3	1.7 mIU/mL Standard Deviation 0.5

SECONDARY outcome

Timeframe: baseline only

Serum will be collected at the first study visit prior to randomization. Total testosterone by mass spectroscopy will be measured.

Outcome measures

Measure	Testosterone Treatment n=6 Participants 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.	No Treatment n=8 Participants Subjects will not receive any testosterone during the study period.
Serum Total Testosterone	181 ng/dl Standard Deviation 100	166 ng/dl Standard Deviation 30

SECONDARY outcome

Timeframe: 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.

Serum will be collected at the first study visit prior to randomization. Inhibin B levels will be measured.

Outcome measures

Measure	Testosterone Treatment n=8 Participants 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.	No Treatment n=6 Participants Subjects will not receive any testosterone during the study period.
Serum Inhibin B (INHB)	244 pg/ml Standard Deviation 96	355 pg/ml Standard Deviation 151

SECONDARY outcome

Timeframe: 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.

Serum will be collected at the first study visit prior to randomization. AMH levels will be measured.

Outcome measures

Measure	Testosterone Treatment n=6 Participants 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.	No Treatment n=8 Participants Subjects will not receive any testosterone during the study period.
Serum Anti-Mullerian Hormone (AMH)	1377 pmol/l Standard Deviation 688	2208 pmol/l Standard Deviation 862

SECONDARY outcome

Timeframe: baseline only

Population: Unable to be analyzed due to insufficient quantities of serum collected. Prioritized hormone assays first.

Serum will be collected at the first study visit prior to randomization. Leptin levels will be measured.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Testosterone Treatment n=10 Participants 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.	No Treatment n=10 Participants Subjects will not receive any testosterone during the study period.
Change in Raw Score on the Alberta Infant Motor Scale	10.5 raw score Standard Deviation 4.9	8.9 raw score Standard Deviation 7.1

SECONDARY outcome

Timeframe: 3 months

Population: Data for this measurement was not collected for any of the participants.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Testosterone Treatment n=10 Participants 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.	No Treatment n=10 Participants Subjects will not receive any testosterone during the study period.
Change in Total Motor Standard Score on the Peabody Developmental Motor Scales 2	2.8 change in standard score Standard Deviation 7.3	2.0 change in standard score Standard Deviation 6.9

SECONDARY outcome

Timeframe: Baseline and 3 months

Stretched penile length will be measured by a physician before randomization and at the end of the study period.

Outcome measures

Measure	Testosterone Treatment n=10 Participants 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.	No Treatment n=10 Participants Subjects will not receive any testosterone during the study period.
Change in Penile Length	0.9 cm Standard Deviation 0.5	-0.3 cm Standard Deviation 0.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Testosterone Treatment n=10 Participants 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.	No Treatment n=10 Participants Subjects will not receive any testosterone during the study period.
Change in Fat Free Mass	1.4 kg Standard Deviation 0.4	0.6 kg Standard Deviation 0.3

Adverse Events

Testosterone Treatment

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Testosterone Treatment n=10 participants at risk 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.
Skin and subcutaneous tissue disorders Acne	20.0% 2/10 • 3 months Adverse events were captured by parental report in the active treatment arm only. All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed for the 'No Treatment' Arm/Group
Gastrointestinal disorders Change in diet or elimination habits	20.0% 2/10 • 3 months Adverse events were captured by parental report in the active treatment arm only. All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed for the 'No Treatment' Arm/Group
Reproductive system and breast disorders Erections	30.0% 3/10 • 3 months Adverse events were captured by parental report in the active treatment arm only. All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed for the 'No Treatment' Arm/Group
General disorders Mood change	10.0% 1/10 • 3 months Adverse events were captured by parental report in the active treatment arm only. All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed for the 'No Treatment' Arm/Group

Additional Information

Dr. Shanlee Davis

University of Colorado

Phone: 720-777-6073

Email: shanlee.davis@childrenscolorado.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place