Klinefelter SyndromePhase 4TESTONCT03325647
TESTO: Testosterone Effects on Short-Term Outcomes in Infants With XXY
A Phase 4 study testing Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution in people with Klinefelter Syndrome, run by University of Colorado, Denver at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 31 to 90 days, men only
- Conditions the study is for
- Klinefelter Syndrome
- What is being tested?
- Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Nov 2017to 5 May 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 31 to 90 days
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Male infants with 47,XXY karyotype identified prenatally who are 4-12 weeks old (31 to 90 days of age). 47,XXY must be from a diagnostic test such as Chorionic Villus Sampling (CVS), amniocentesis, or post-natal blood/tissue. Non-invasive prenatal screening results alone will not be accepted.
Who cannot join
- >20 percent mosaicism for a normal cell line
- Gestational age at birth <36 weeks
- Birth weight <2.5th percentile or >97.5 percentile for age (small or large for gestational age)
- History of thrombosis in self or a first degree relative
- Exposure to androgen therapy outside the study protocol
- Use of medications known to affect body composition, such as growth hormone or insulin
- Known allergy to the testosterone cypionate solution components including benzyl benzoate, benzyl alcohol, or cottonseed oil
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Colorado
Aurora, Colorado, 80045
About this study
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.
Read the detailed description
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.
- Conditions
- Klinefelter Syndrome
- Being tested
- Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution, Placebo injectable saline
- Keywords
- body composition, klinefelter syndrome, XXY, sex chromosome variation, sex chromosome aneuploidy, testosterone
- Medical subject headings
- Klinefelter Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone Cypionate 200 Milligram/Milliliter Injectable SolutionDrug
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.
Placebo injectable salineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Visit 1 Drug, Visit 2 Placebo | Experimental | 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. Receives: Drug: Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution; Drug: Placebo injectable saline |
| Visit 1 Placebo, Visit 2 Drug | Experimental | 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. Receives: Drug: Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution; Drug: Placebo injectable saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: Baseline and 3 months
Secondary outcomes (20)
Change in height
Physical exam measurements will be measured by a physician at each visit
Measured: 6 months
Change in weight
Physical exam measurements will be measured by a physician at each visit
Measured: 6 months
Change in weight-for-length
Physical exam measurements will be measured by a physician at each visit
Measured: 6 months
Change in waist circumference
Physical exam measurements will be measured by a physician at each visit
Measured: 6 months
Change in serum leptin
Serum will be collected and measured at each study visit.
Measured: 6 months
Change in lipids
Serum will be collected and measured at each study visit.
Measured: 6 months
Change in insulin
Serum will be collected and measured at each study visit.
Measured: 6 months
Change in serum Luteinizing Hormone (LH)
Serum will be collected at each study visit. Ultrasensitive LH will be measured.
Measured: 6 months
Change in serum Follicle Stimulating Hormone (FSH)
Serum will be collected at each study visit. Follicle Stimulating Hormone (FSH) will be measured.
Measured: 6 months
Change in Inhibin B (INHB)
Inhibin B levels will be measured.
Measured: 6 months
Change in Anti-Mullerian Hormone (AMH)
Serum will be collected at each study visit. AMH levels will be measured.
Measured: 6 months
Change in Total Testosterone (Total T)
Serum will be collected at each study visit. Total testosterone by mass spectroscopy will be measured.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months
Change in Number and Type of Adverse Events
Adverse events will be measured by verbal questionnaire and parent-report, to determine safety.
Measured: 6 months
Change in Serum BCAA, other LCAC
BCAA and other LCAC will be measured through targeted metabolomics from serum collection at each visit.
Measured: 6 months
Change in Pathway analysis
Serum Pathways will be measured through untargeted/unbiased metabolomics
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2017
- Study start6 Nov 2017
- Primary completion5 May 2021
- Study completion5 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Klinefelter SyndromeStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Shanlee M Davis, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03325647
- Sponsor's protocol ID
- 17-1317
- Other IDs
- 5K23HD092588-02
- Acronym
- TESTO
- Status last verified
- Apr 2022
- First submitted
- 16 Oct 2017
- Last updated
- 6 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TESTO: Testosterone Effects on Short-Term Outcomes in Infants With XXY
- ClinicalTrials.gov ID
- NCT03325647
- Acronym / sponsor ID
- TESTO / 17-1317
- Conditions
- Klinefelter Syndrome
- Keywords
- body composition, klinefelter syndrome, XXY, sex chromosome variation, sex chromosome aneuploidy, testosterone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 6 Nov 2017 (actual)
- Primary completion
- 5 May 2021 (actual)
- Study completion
- 5 May 2021 (actual)
- First posted
- 30 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Visit 1 Drug, Visit 2 Placebo | Experimental | Drug: Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution, Drug: Placebo injectable salineSubjects 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. |
| Visit 1 Placebo, Visit 2 Drug | Experimental | Drug: Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution, Drug: Placebo injectable salineSubjects 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. |
Who may qualify
- Ages
- 31 to 90 days
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Male infants with 47,XXY karyotype identified prenatally who are 4-12 weeks old (31 to 90 days of age). 47,XXY must be from a diagnostic test such as Chorionic Villus Sampling (CVS), amniocentesis, or post-natal blood/tissue. Non-invasive prenatal screening results alone will not be accepted.
Key exclusion criteria (7 listed)
- >20 percent mosaicism for a normal cell line
- Gestational age at birth <36 weeks
- Birth weight <2.5th percentile or >97.5 percentile for age (small or large for gestational age)
- History of thrombosis in self or a first degree relative
- Exposure to androgen therapy outside the study protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Testosterone Cypionate 200 Milligram/Milliliter Injectable SolutionSubjects 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. | Drug | Visit 1 Drug, Visit 2 Placebo, Visit 1 Placebo, Visit 2 Drug |
| Placebo injectable salineSubjects 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. | Drug | Visit 1 Drug, Visit 2 Placebo, Visit 1 Placebo, Visit 2 Drug |
Primary outcome
Change in Body Fat Percentage
Time frame: 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
Change in Composite Motor Score on Alberta Infant Motor Scale
Time frame: 3 months
Motor development will be assessed using the standardized Alberta Infant Motor Scale
Change in C14:1 Long Chain Acylcarnitines (LCAC) through targeted metabolomics
Time frame: Baseline and 3 months
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.
20 secondary outcomes
Change in height
Time frame: 6 months
Change in weight
Time frame: 6 months
Change in weight-for-length
Time frame: 6 months
Change in waist circumference
Time frame: 6 months
Change in serum leptin
Time frame: 6 months
Change in lipids
Time frame: 6 months
Change in insulin
Time frame: 6 months
Change in serum Luteinizing Hormone (LH)
Time frame: 6 months
Change in serum Follicle Stimulating Hormone (FSH)
Time frame: 6 months
Change in Inhibin B (INHB)
Time frame: 6 months
Change in Anti-Mullerian Hormone (AMH)
Time frame: 6 months
Change in Total Testosterone (Total T)
Time frame: 6 months
Change in Gross Motor Scores on the Peabody Developmental Motor Scales 2
Time frame: 6 months
Change in Gross Motor Scores on the Alberta Infant Motor Scales
Time frame: 6 months
Change in Fine Motor Scores
Time frame: 6 months
Change in Cognitive and Language Composite Scores on the Bayley III
Time frame: 6 months
Change in Adaptive Functioning
Time frame: 6 months
Change in Number and Type of Adverse Events
Time frame: 6 months
Change in Serum BCAA, other LCAC
Time frame: 6 months
Change in Pathway analysis
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shanlee M Davis, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution in people with Klinefelter Syndrome, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Body Fat Percentage (time frame: Baseline and 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2022.