A Phase 4 interventional study of Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution and Placebo injectable saline in Klinefelter Syndrome, sponsored by University of Colorado, Denver. Completed at 1 site in United States. Open to male participants aged 31 Days to 90 Days. Per ClinicalTrials.gov, last updated 2022-05-06.
Sponsored by University of Colorado, Denver · Phase 4, Interventional, and Treatment
This research study in infant males with Klinefelter syndrome (47,XXY) will learn more about the effect of testosterone on early health and development. The study is a total of three visits over 6 months with assessments of motor skills, body composition (muscle and fat), and hormone levels. This is a randomized, placebo-controlled study but all infants will receive testosterone treatment during the study period. The investigators will learn how testosterone treatment in infancy effects short term outcome measures on health and development.
XXY (also known as Klinefelter syndrome) is the most common chromosomal abnormality in males, affecting 1/600 boys. The extra X chromosome leads to insufficient development of the testicles and subsequent testosterone deficiency. Males with XXY also have a high risk for developmental delays, learning disabilities, and cardiovascular disease. An essential question is how much of this risk is because of testosterone deficiency and could therefore be reduced by testosterone supplementation, particularly during critical periods of development.
In typical male development, there is a surge of testosterone in the first few months of life, commonly known as the "mini-puberty period of infancy." This testosterone surge may be critical for neurodevelopmental and cardiometabolic programming throughout life. Recently there has been increased off-label use of testosterone in infants with XXY, however neither the short or long term safety or efficacy have been evaluated. This study aims to quantify the short term effects of testosterone treatment in infants with XXY on neurodevelopment, growth, body composition, testicular function, and safety parameters. This is a double blind randomized placebo controlled trial of testosterone injections 25 mg every 4 weeks for 3 doses in boys with XXY enrolled between 1 and 3 months of age. Outcomes including body fat percentage, scaled motor developmental scores, growth velocity, testicular hormone concentrations, specific metabolites, and safety parameters will be assessed 12 weeks into the study. The groups will then cross-over (all subjects will receive testosterone during the study period) and the outcomes will be reassessed 24 weeks into the study. The secondary questions the investigators will answer with this cross-over is 1) whether benefits in the treatment group at 12 weeks are sustained at 24 weeks, and 2) whether the same benefits are seen if treated after the mini-puberty period.
45 studies on the registry are indexed under Klinefelter Syndrome; 15 are open to participants now.
This study's enrollment of 72 is above the median of 44 across 19 interventional studies indexed under Klinefelter Syndrome.
Browse Klinefelter Syndrome studies →University of Colorado, Denver is the lead sponsor of 1,538 studies on the registry; 318 are open to participants now.
Of its 146 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
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Exclusion Criteria:
Subjects in this group will be randomized to receive Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution every 4 weeks x 3 doses, beginning at visit 1, and Placebo Injectable Saline beginning at visit 2.
Drug: Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution · Drug: Placebo injectable saline
Subjects in this group will be randomized to receive Placebo Injectable Saline beginning at visit 1, and Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution every 4 weeks x 3 doses beginning at visit 2.
Drug: Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution · Drug: Placebo injectable saline
Subjects in one arm will be randomized to receive testosterone cypionate 200 mg/ml intramuscularly every 4 weeks for a total of three doses after visit 1, and receive placebo injectable saline for the same duration starting at visit 2. Subjects in the other arm will be randomized to receive placebo injectable saline every 4 weeks for a total of 3 doses after visit 1, and testosterone cypionate 200 mg/ml intramuscularly for the same duration starting at visit 2.
Subjects in one arm will be randomized to receive testosterone cypionate 200 mg/ml intramuscularly every 4 weeks for a total of three doses after visit 1, and receive placebo injectable saline for the same duration starting at visit 2. Subjects in the other arm will be randomized to receive placebo injectable saline every 4 weeks for a total of 3 doses after visit 1, and testosterone cypionate 200 mg/ml intramuscularly for the same duration starting at visit 2.
Change in Body Fat Percentage
Body fat percentage will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period
Time frame: Baseline and 3 months
Change in Composite Motor Score on Alberta Infant Motor Scale
Motor development will be assessed using the standardized Alberta Infant Motor Scale
Time frame: 3 months
Change in C14:1 Long Chain Acylcarnitines (LCAC) through targeted metabolomics
Plasma will be processed and stored until batch analysis using electrospray tandem mass spectroscopy per standard protocols to quantify acylcarnitines (short, medium, and long-chain) and Branched-Chain Amino Acids (BCAA--leucine/isoleucine and valine) at baseline and 12 weeks.
Time frame: Baseline and 3 months
Change in height
Physical exam measurements will be measured by a physician at each visit
Time frame: 6 months
Change in weight
Physical exam measurements will be measured by a physician at each visit
Time frame: 6 months
Change in weight-for-length
Physical exam measurements will be measured by a physician at each visit
Time frame: 6 months
Change in waist circumference
Physical exam measurements will be measured by a physician at each visit
Time frame: 6 months
Change in serum leptin
Serum will be collected and measured at each study visit.
Time frame: 6 months
Change in lipids
Serum will be collected and measured at each study visit.
Time frame: 6 months
Change in insulin
Serum will be collected and measured at each study visit.
Time frame: 6 months
Change in serum Luteinizing Hormone (LH)
Serum will be collected at each study visit. Ultrasensitive LH will be measured.
Time frame: 6 months
Change in serum Follicle Stimulating Hormone (FSH)
Serum will be collected at each study visit. Follicle Stimulating Hormone (FSH) will be measured.
Time frame: 6 months
Change in Inhibin B (INHB)
Inhibin B levels will be measured.
Time frame: 6 months
Change in Anti-Mullerian Hormone (AMH)
Serum will be collected at each study visit. AMH levels will be measured.
Time frame: 6 months
Change in Total Testosterone (Total T)
Serum will be collected at each study visit. Total testosterone by mass spectroscopy will be measured.
Time frame: 6 months
Change in Gross Motor Scores on the Peabody Developmental Motor Scales 2
Gross motor development will be assessed using the standardized Peabody Developmental Motor Scales 2. The Peabody Developmental Motor Scales 2 measures gross motor development using the subscale of the Gross Motor Quotient, which measures the ability to utilize the large muscle systems. High scores on this composite are made by children with well-developed gross motor abilities.
Time frame: 6 months
Change in Gross Motor Scores on the Alberta Infant Motor Scales
Gross motor development will be assessed using the standardized Alberta Infant Motor Scales (AIMS). The Alberta Infant Motor Scales is a performance-based and norm-referenced measure of infant gross motor maturation from birth to 18 months. The AIMS total score is calculated by summing the scores for the 58 items, with the score ranging between 0 and 58. Higher scores indicate more mature motor development. The infant's score can then be converted to a percentile and compared with age-equivalent peers from the normative sample.
Time frame: 6 months
Change in Fine Motor Scores
Fine motor development will be assessed using the standardized Peabody Developmental Motor Scales 2. The Peabody Developmental Motor Scales 2 measures fine motor development using subscale of the Fine Motor Quotient, which measures a child's ability to use his or her hands and arms to grasp objects, stack blocks, draw figures, and manipulate objects. High scores on this composite are made by children with well-developed fine motor abilities.
Time frame: 6 months
Change in Cognitive and Language Composite Scores on the Bayley III
Cognition and language will be assessed by a trained administrator of developmental tests using the standardized Bayley Scales of Infant and Toddler Development III: cognitive and language domains. In each subscale, age-standardized scores are calculated using test norms. Developmental delay is determined by calculating how many standard deviations a child scores from the mean in that subscale. Typically, the more standard deviations below the mean, the more severe the delay.
Time frame: 6 months
Change in Adaptive Functioning
Adaptive Functioning will be assessed using the Adaptive Behavior Assessment System, 3rd edition, completed by the parent about their child.
Time frame: 6 months
Change in Number and Type of Adverse Events
Adverse events will be measured by verbal questionnaire and parent-report, to determine safety.
Time frame: 6 months
Change in Serum BCAA, other LCAC
BCAA and other LCAC will be measured through targeted metabolomics from serum collection at each visit.
Time frame: 6 months
Change in Pathway analysis
Serum Pathways will be measured through untargeted/unbiased metabolomics
Time frame: 3 months
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Plan to share: No
Ran from Nov 2017 to primary completion in May 2021, 41 months.
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