Klinefelter SyndromeTestoXXY/KSNCT01585831
Study of Psychological and Motor Effects of Testosterone in Adolescents With XXY/Klinefelter Syndrome
A study testing Testosterone gel 1% in people with Klinefelter Syndrome and XXY Syndrome, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to determine if testosterone replacement therapy leads to changes in psychological factors and/or motor skills in adolescent males with 47,XXY (also called Klinefelter syndrome). Read more about this study
- Who is it for?
- Ages 8 to 18 years, men only
- Conditions the study is for
- Klinefelter Syndrome, XXY Syndrome
- What is being tested?
- Testosterone gel 1%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Oct 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 8 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Males with 47,XXY
- Participants must be in early puberty (Tanner stage II-III)
- Age 8 - 18 will be considered, but eligibility will be determined by review of laboratory results, bone age X-ray, and physical examination to determine stage of puberty
- All racial and ethnic groups
Who cannot join
- Other genetic variations of Klinefelter syndrome (48,XXXY, 48,XXYY, 49,XXXXY). The investigator has other studies for these groups and we encourage interested individuals with these disorders to contact us about other available studies.
- 47,XXY plus another genetic disorder
- Non-English speaking individuals (because the psychological tests are administered in English)
- Participants with a medical history of blood clotting problems, blindness, deafness, or cancer
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Psychological and Motor Effects of Testosterone Therapy in Adolescents With XXY/Klinefelter Syndrome
The purpose of this study is to determine if testosterone replacement therapy leads to changes in psychological factors and/or motor skills in adolescent males with 47,XXY (also called Klinefelter syndrome). This study will also evaluate whether certain genetic factors of the X chromosome affect the psychological or motor features of XXY/Klinefelter syndrome.
Read the detailed description
Klinefelter syndrome (47,XXY) is the most common chromosomal abnormality in humans and occurs in approximately 1 in 650 males. Testosterone deficiency develops during adolescence in the majority of individuals with XXY. However, there are no previous studies that evaluate the psychological and motor effects of testosterone replacement therapy in adolescents with XXY.
The study researchers are interested in learning if testosterone therapy initiated in early puberty in XXY (KS) will lead to improvements in psychological and/or motor skills. They are also interested in learning if genetic variations of the androgen receptor gene or the parent-of-origin of the extra X chromosome influence the response to testosterone therapy.
Specific psychological factors to be studied include verbal and nonverbal cognitive skills, attention, executive function (organization, problem-solving skills, inhibition), anxiety, language, self-esteem, and other behavioral factors. Motor skills to be studied include gross and fine motor skills, motor coordination, and motor planning.
Participants in the study will be randomized to one of two treatment groups, receiving either testosterone gel or placebo, for 12 months. 60% of the study group will receive testosterone, and 40% will receive placebo.
The research participants, parents/caregivers, and the members of the study team will be blinded to the treatment group, and will not know whether they are receiving testosterone gel or placebo treatments.
The supervising endocrinologist for the study will not be blinded and will know which patients are in the testosterone and placebo groups. This will allow him to monitor results to determine if participants in the placebo group may develop a significant need for testosterone therapy during the study period. If this occurs, the patient will be switched to the testosterone group and will continue to be monitored in the study.
All participants will be evaluated at the beginning of the study and at 1, 3, 6, and 12 months. Travel costs are included. Evaluations will include a combination of psychological and motor skills testing, questionnaires completed by the parent/caregiver and study participant, physical examinations, and blood draws for safety monitoring and genetic studies.
Participation in the trial will last one year and includes 5 clinic visits to the eXtraordinarY Kids Clinic at Children's Hospital Colorado in Denver.
- Conditions
- Klinefelter Syndrome, XXY Syndrome
- Being tested
- Testosterone gel 1%, Placebo gel
- Keywords
- Klinefelter syndrome, XXY syndrome, Sex Chromosome Abnormality, Testosterone replacement therapy
- Medical subject headings
- Klinefelter Syndrome, Sex Chromosome Aberrations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone gel 1%Drug
Also called Androgel 1%
Testosterone gel will be administered on a daily basis. The gel will be dispensed in a syringe, and the specific amount of gel to be applied each day will be determined by the study endocrinologist after reviewing labs.
Placebo gelDrug
The placebo gel will be administered on a daily basis. The gel will be dispensed in a syringe, and the specific amount of gel to be applied each day will be determined by the study endocrinologist.
| Study group | Role | What they receive |
|---|---|---|
| Testosterone gel 1% | Experimental | Testosterone gel 1% applied to skin once per day for 1 year. Starting dose 1.25mL per day, titrated in 1.25mL increments for 1st 6 months of study after each study visit up to maximum of 5.0mL per day. Titration based on testosterone levels with target level in mid-range of normal for Tanner stage. Receives: Drug: Testosterone gel 1% |
| Placebo gel | Placebo comparator | Placebo gel applied to skin once per day for 1 year. Starting dose 1.25mL per day. Dose randomly adjusted in 1.25mL increments for 1st 6 months of study after each study visit up to maximum of 5.0mL per day. Receives: Drug: Placebo gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline on the Delis-Kaplan Executive Function System
A collection of subtests from the Delis-Kaplan Executive Function System will be used to evaluate different domains of executive functions including planning, problem solving, fluency, inhibition, and working memory. Possible scaled scores range from 0-20 (mean of 10), with higher scores indicating better performance. The value of the change in scaled score from baseline is reported.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Bruininks-Oseretsky Test of Motor Development - 2
This test evaluates many aspects of motor functioning including fine and gross motor skills, visual motor integration, motor planning, and motor coordination. Possible scores range from 20-80, with higher scores indicating a better outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Conners Parent Rating Scales: DSM Attention
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100 (Mean T-score 50), with higher scores indicating a worse outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Conners Parent Rating Scales: DSM Hyperactivity
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100 (Mean T-score 50), with higher scores indicating a worse outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Conners Parent Rating Scales: Anxiety
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100 (Mean T-score 50), with higher scores indicating a worse outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Conners Parent Rating Scales: Social Skills
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100, with higher scores indicating a worse outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Conners Parent Rating Scales: Emotional Lability
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100, with higher scores indicating a worse outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Secondary outcomes (3)
Change From Baseline on the Vineland Adaptive Behavior Scales - 2nd Edition
The Vineland-2 is an interview evaluating adaptive skills in the areas of communication, daily living skills, social skills, and motor skills. Possible scores range from 20 to 160 (mean 100), with higher scores indicating a better outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Wechsler Intelligence Scale for Children - Fourth Edition
This standardized assessment of cognitive functioning allows for evaluation of verbal and nonverbal cognitive skills, working memory, and processing speed. Possible full scale IQ scores range from 40-180 (mean 100), with higher scores indicating a better outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Comprehensive Test of Phonological Processing
This standardized test evaluates reading and language skills. Possible scores range from 20-200 (Mean Standard Score 100), with higher scores indicating a better outcome.
Measured: Visit 1 (baseline) and Visit 5 (1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2012 (estimated)
- Study startMar 2012
- Primary completionOct 2017
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Colorado Clinical & Translational Sciences Institute, Children's Hospital Colorado, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
- Investigators
- Nicole Tartaglia, MD, Principal investigator, University of Colorado School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01585831
- Sponsor's protocol ID
- 11-0874
- Other IDs
- 1K23NS070337
- Acronym
- TestoXXY/KS
- Status last verified
- Jul 2021
- First submitted
- 30 Mar 2012
- Last updated
- 10 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Davis SM, DeKlotz S, Nadeau KJ, Kelsey MM, Zeitler PS, Tartaglia NR. High prevalence of cardiometabolic risk features in adolescents with 47,XXY/Klinefelter syndrome. Am J Med Genet C Semin Med Genet. 2020 Jun;184(2):327-333. doi: 10.1002/ajmg.c.31784. Epub 2020 Jun 16.
PubMed 32542985
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psychological and Motor Effects of Testosterone Therapy in Adolescents With XXY/Klinefelter Syndrome
- ClinicalTrials.gov ID
- NCT01585831
- Acronym / sponsor ID
- TestoXXY/KS / 11-0874
- Conditions
- Klinefelter Syndrome, XXY Syndrome
- Keywords
- Klinefelter syndrome, XXY syndrome, Sex Chromosome Abnormality, Testosterone replacement therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Colorado Clinical & Translational Sciences Institute, Children's Hospital Colorado, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Mar 2012
- Primary completion
- Oct 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 26 Apr 2012 (estimated)
- Results
- Posted 10 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if testosterone replacement therapy leads to changes in psychological factors and/or motor skills in adolescent males with 47,XXY (also called Klinefelter syndrome). This study will also evaluate whether certain genetic factors of the X chromosome affect the psychological or motor features of XXY/Klinefelter syndrome.
Detailed description
Klinefelter syndrome (47,XXY) is the most common chromosomal abnormality in humans and occurs in approximately 1 in 650 males. Testosterone deficiency develops during adolescence in the majority of individuals with XXY. However, there are no previous studies that evaluate the psychological and motor effects of testosterone replacement therapy in adolescents with XXY.
The study researchers are interested in learning if testosterone therapy initiated in early puberty in XXY (KS) will lead to improvements in psychological and/or motor skills. They are also interested in learning if genetic variations of the androgen receptor gene or the parent-of-origin of the extra X chromosome influence the response to testosterone therapy.
Specific psychological factors to be studied include verbal and nonverbal cognitive skills, attention, executive function (organization, problem-solving skills, inhibition), anxiety, language, self-esteem, and other behavioral factors. Motor skills to be studied include gross and fine motor skills, motor coordination, and motor planning.
Participants in the study will be randomized to one of two treatment groups, receiving either testosterone gel or placebo, for 12 months. 60% of the study group will receive testosterone, and 40% will receive placebo.
The research participants, parents/caregivers, and the members of the study team will be blinded to the treatment group, and will not know whether they are receiving testosterone gel or placebo treatments.
The supervising endocrinologist for the study will not be blinded and will know which patients are in the testosterone and placebo groups. This will allow him to monitor results to determine if participants in the placebo group may develop a significant need for testosterone therapy during the study period. If this occurs, the patient will be switched to the testosterone group and will continue to be monitored in the study.
All participants will be evaluated at the beginning of the study and at 1, 3, 6, and 12 months. Travel costs are included. Evaluations will include a combination of psychological and motor skills testing, questionnaires completed by the parent/caregiver and study participant, physical examinations, and blood draws for safety monitoring and genetic studies.
Participation in the trial will last one year and includes 5 clinic visits to the eXtraordinarY Kids Clinic at Children's Hospital Colorado in Denver.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Testosterone gel 1% | Experimental | Drug: Testosterone gel 1%Testosterone gel 1% applied to skin once per day for 1 year. Starting dose 1.25mL per day, titrated in 1.25mL increments for 1st 6 months of study after each study visit up to maximum of 5.0mL per day. Titration based on testosterone levels with target level in mid-range of normal for Tanner stage. |
| Placebo gel | Placebo comparator | Drug: Placebo gelPlacebo gel applied to skin once per day for 1 year. Starting dose 1.25mL per day. Dose randomly adjusted in 1.25mL increments for 1st 6 months of study after each study visit up to maximum of 5.0mL per day. |
Who may qualify
- Ages
- 8 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Males with 47,XXY
- Participants must be in early puberty (Tanner stage II-III)
- Age 8 - 18 will be considered, but eligibility will be determined by review of laboratory results, bone age X-ray, and physical examination to determine stage of puberty
- All racial and ethnic groups
Key exclusion criteria (4 listed)
- Other genetic variations of Klinefelter syndrome (48,XXXY, 48,XXYY, 49,XXXXY). The investigator has other studies for these groups and we encourage interested individuals with these disorders to contact us about other available studies.
- 47,XXY plus another genetic disorder
- Non-English speaking individuals (because the psychological tests are administered in English)
- Participants with a medical history of blood clotting problems, blindness, deafness, or cancer
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 gel 1%Also: Androgel 1%Testosterone gel will be administered on a daily basis. The gel will be dispensed in a syringe, and the specific amount of gel to be applied each day will be determined by the study endocrinologist after reviewing labs. | Drug | Testosterone gel 1% |
| Placebo gelThe placebo gel will be administered on a daily basis. The gel will be dispensed in a syringe, and the specific amount of gel to be applied each day will be determined by the study endocrinologist. | Drug | Placebo gel |
Primary outcome
Change From Baseline on the Delis-Kaplan Executive Function System
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
A collection of subtests from the Delis-Kaplan Executive Function System will be used to evaluate different domains of executive functions including planning, problem solving, fluency, inhibition, and working memory. Possible scaled scores range from 0-20 (mean of 10), with higher scores indicating better performance. The value of the change in scaled score from baseline is reported.
Change From Baseline on the Bruininks-Oseretsky Test of Motor Development - 2
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
This test evaluates many aspects of motor functioning including fine and gross motor skills, visual motor integration, motor planning, and motor coordination. Possible scores range from 20-80, with higher scores indicating a better outcome.
Change From Baseline on the Conners Parent Rating Scales: DSM Attention
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100 (Mean T-score 50), with higher scores indicating a worse outcome.
Change From Baseline on the Conners Parent Rating Scales: DSM Hyperactivity
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100 (Mean T-score 50), with higher scores indicating a worse outcome.
Change From Baseline on the Conners Parent Rating Scales: Anxiety
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100 (Mean T-score 50), with higher scores indicating a worse outcome.
Change From Baseline on the Conners Parent Rating Scales: Social Skills
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100, with higher scores indicating a worse outcome.
Change From Baseline on the Conners Parent Rating Scales: Emotional Lability
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
This questionnaire allows parents to rate many aspects of behavior including attention, hyperactivity, anxiety, social skills, and emotional lability. The range of possible scores is 0 to 100, with higher scores indicating a worse outcome.
3 secondary outcomes
Change From Baseline on the Vineland Adaptive Behavior Scales - 2nd Edition
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Wechsler Intelligence Scale for Children - Fourth Edition
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
Change From Baseline on the Comprehensive Test of Phonological Processing
Time frame: Visit 1 (baseline) and Visit 5 (1 year)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32542985Davis SM, DeKlotz S, Nadeau KJ, Kelsey MM, Zeitler PS, Tartaglia NR. High prevalence of cardiometabolic risk features in adolescents with 47,XXY/Klinefelter syndrome. Am J Med Genet C Semin Med Genet. 2020 Jun;184(2):327-333. doi: 10.1002/ajmg.c.31784. Epub 2020 Jun 16.
- KS\&A supports individuals with XXY/Klinefelter syndrome and other X\&Y chromosome variationsLink provided by the sponsor.
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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.
Nicole Tartaglia, MD principal investigator
University of Colorado School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Testosterone gel 1% in people with Klinefelter Syndrome and XXY 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 4 inclusion and 4 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 10 Aug 2021. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 From Baseline on the Delis-Kaplan Executive Function System (time frame: Visit 1 (baseline) and Visit 5 (1 year)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01585831, which also lists 1 linked publication.
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 10 Aug 2021.