Klinefelter SyndromePhase 2NCT00348946
Androgen Effect on Klinefelter Syndrome Motor Outcome
A Phase 2 study testing androgen oxandrolone in people with Klinefelter Syndrome, run by Thomas Jefferson University at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the effects of low-dose androgen on the motor and cognitive development of boys with Klinefelter syndrome. Read more about this study
- Who is it for?
- Ages 4 to 12 years, men only
- Conditions the study is for
- Klinefelter Syndrome
- What is being tested?
- androgen oxandrolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 93 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to 30 Nov 2017
- Phase
- Phase 2
- 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 4 to 12 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Karyotype diagnosis of Klinefelter syndrome
- Chronological age of 4-12 years
- No treatment with androgen in the past year
Who cannot join
- Major liver, kidney or other systemic disease
- Variant karyotypes including 47,XYY males
- Evidence of spontaneous onset of puberty, defined as testicular size > 4ml
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University, Department of Pediatrics, 1025 Walnut Street, Suite 726
Philadelphia, Pennsylvania, 19107
About this study
Official title: Androgen Effect on Motor/Cognitive Outcome in Klinefelter Syndrome
The purpose of this study is to evaluate the effects of low-dose androgen on the motor and cognitive development of boys with Klinefelter syndrome.
Read the detailed description
Klinefelter syndrome (KS), a genetic disorder that affects males only, is characterized by having an extra X chromosome. The phenotype - or physical and learning features - includes testicular failure, tall stature, and specific cognitive and behavioral attributes such as diminished motor function, language-based learning difficulties, poor self-image, and shyness. The KS phenotype may be the result of androgen deficiency in utero, infancy, and childhood. For individuals with KS, androgen replacement is standard treatment in adolescence and adulthood but has not been used earlier in childhood or included in the standard medical care of KS children ages 4 to 12.
The purpose of this study is to examine the effects of androgen on learning and development in boys with KS. Researchers also want to determine if low-dose androgen replacement at an early age will improve some of the learning difficulties associated with the disorder. The overall goal of this study is to address questions regarding the relationship of early androgen deficiency to learning and motor function.
Participants in the study will be randomized to one of two treatment groups, receiving either oxandrolone (low-dose androgen) or placebo, for two years. All participants will be evaluated for safety at the beginning of the study and at 3, 6, 12, 18, and 24 months. Also at the beginning of the study and every 3 to 6 months thereafter (for a total of 6 visits), the researchers will perform a careful history and physical examination and a bone age X-ray, and obtain a blood sample.
Participation in the trial will last two years and includes 6 clinic visits.
- Conditions
- Klinefelter Syndrome
- Being tested
- androgen oxandrolone, placebo
- Keywords
- Klinefelter syndrome, androgen, androgen oxandrolone
- Medical subject headings
- Klinefelter Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
androgen oxandroloneDrug
Oxandrolone ,06 >mg/kg/day, orally, for 2 years
placeboOther
an inactive substance
| Study group | Role | What they receive |
|---|---|---|
| Oxandrolone | Active comparator | Androgen oxandrolone: Oxandrolone, 0.6 > mg/kg/day, orally, for 2 years. Receives: Drug: androgen oxandrolone |
| Placebo | Placebo comparator | An inactive substance. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motor Function/Strength
Outcome measures were tested using the following assessments: Bruininks-Osertesky Test of Motor Proficiency (BOT) subscales of (1) Visual Motor Control, (2) Upper limb Speed, and (3) Strength, Physical and Neurological Evaluation for Soft Signs (PANESS), and Hand Strength Dynamometer. BOT assess the child's motor development and includes standard scores (mean=100, SD=15) and subtest scores and is normed for sex and age (4-14.5 years). PANESS assesses the time required to press thumb to 4 fingers 20 times for the dominant and nondominant hands and includes standard scores (mean=100, SD=15) with age-specific norms (4-18 years). Hand strength dynamometer assess hand strength in the dominant and nondominant hands and includes standard scores (mean=100, SD=15). Data is expressed as standard scores with mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scorers imply better function.
Measured: 2 years per subject
Secondary outcomes (4)
Cognitive Function and Language
Outcome measures were tested using the Differential Ability Scales - 2nd edition (DAS-II). DAS-II provides an age- and sex-standardized assessment of intellectual functioning (General Concept Ability subscale similar to IQ) in children ages 2-17 years of age (mean=100, SD=15). The Verbal Cluster measures the child's ability to define words and perform verbal reasoning tasks. The Nonverbal Cluster measures the child's inductive and sequential reasoning abilities. The Spatial Cluster measures visuospatial construction ability, spatial memory, and spatial reasoning. Data is expressed as standard scores with mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scores imply better function.
Measured: 2 years per subject
Working Memory/Attention
Outcome measures were tested using the following cognitive assessments: Digit Span Backward, A Neuropsychological Assessment (NEPSY) subscales of (1) Phonemic Fluency and (2) Semantic Fluency, and Connors' Continuous Performance Test (CPT-II) subscales (1) Omissions, (2) Commissions, (3) Hit Reaction, (4) Variability, and (5) Preservations. Digit Span Backward tests working memory and is normed for children ages 5-16 years. Phonemic Fluency measures the number of words that the child can name beginning with the letters F and S (ages 6-12). Semantic Fluency measures the number of words the child can name in the categories food and drink (ages 4-12). CPT-II measures the ability to maintain attention over an extended period of time. All scores are reported as standard scores with a mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scores imply better function.
Measured: 2 years per participant
Psychosocial and Behavior Domain
Outcome measures were tested using the following social assessments: The Child Behavior Checklist (CBCL) and The Children's Depression Inventory (CDI). The CBCL is standardized measure of behavior problems and social competency normed for children ages 4-16. Higher scores indicate more problems, with the cutoff for the clinical range at a t score greater than or equal to 67. The CDI assess cognitive, affective and behavioral signs of depression in children ages 6-17. The CDI total score reflects the presence of overall depressive symptoms. All scores are expressed as t-scores with a mean of 50 and SD of 10. Lower scores imply better function and higher scores indicate more problem behaviors.
Measured: 2 years per participants
Psychosocial and Behavior Domain
Outcome measures were tested using The Piers-Harris Self Concept Scale. Scoring provides a total standard score and scores on six subscales: physical appearance and attributes, freedom from anxiety, intellectual and school status, behavioral adjustment, happiness and satisfaction, and popularity. Subscales are summed and standardized to provide the total standard score with a mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scores imply better function.
Measured: 2 years per subject
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2006 (estimated)
- Study startJul 2006
- Primary completion30 Nov 2017
- Study completion30 Nov 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 (3)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 Thomas Jefferson UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Judith L. Ross, M.D., Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00348946
- Sponsor's protocol ID
- R01NS050597-01A2
- Status last verified
- Jul 2021
- First submitted
- 3 Jul 2006
- Last updated
- 8 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Davis SM, Lahlou N, Cox-Martin M, Kowal K, Zeitler PS, Ross JL. Oxandrolone Treatment Results in an Increased Risk of Gonadarche in Prepubertal Boys With Klinefelter Syndrome. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3449-3455. doi: 10.1210/jc.2018-00682.
PubMed 29931143Ross JL, Kushner H, Kowal K, Bardsley M, Davis S, Reiss AL, Tartaglia N, Roeltgen D. Androgen Treatment Effects on Motor Function, Cognition, and Behavior in Boys with Klinefelter Syndrome. J Pediatr. 2017 Jun;185:193-199.e4. doi: 10.1016/j.jpeds.2017.02.036. Epub 2017 Mar 10.
PubMed 28285751Davis S, Lahlou N, Bardsley M, Temple MC, Kowal K, Pyle L, Zeitler P, Ross J. Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome. Andrology. 2016 Nov;4(6):1169-1177. doi: 10.1111/andr.12275. Epub 2016 Sep 16.
PubMed 27637014
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Androgen Effect on Motor/Cognitive Outcome in Klinefelter Syndrome
- ClinicalTrials.gov ID
- NCT00348946
- Acronym / sponsor ID
- R01NS050597-01A2
- Conditions
- Klinefelter Syndrome
- Keywords
- Klinefelter syndrome, androgen, androgen oxandrolone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jul 2006
- Primary completion
- 30 Nov 2017 (actual)
- Study completion
- 30 Nov 2017 (actual)
- First posted
- 6 Jul 2006 (estimated)
- Results
- Posted 8 Jul 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 evaluate the effects of low-dose androgen on the motor and cognitive development of boys with Klinefelter syndrome.
Detailed description
Klinefelter syndrome (KS), a genetic disorder that affects males only, is characterized by having an extra X chromosome. The phenotype - or physical and learning features - includes testicular failure, tall stature, and specific cognitive and behavioral attributes such as diminished motor function, language-based learning difficulties, poor self-image, and shyness. The KS phenotype may be the result of androgen deficiency in utero, infancy, and childhood. For individuals with KS, androgen replacement is standard treatment in adolescence and adulthood but has not been used earlier in childhood or included in the standard medical care of KS children ages 4 to 12.
The purpose of this study is to examine the effects of androgen on learning and development in boys with KS. Researchers also want to determine if low-dose androgen replacement at an early age will improve some of the learning difficulties associated with the disorder. The overall goal of this study is to address questions regarding the relationship of early androgen deficiency to learning and motor function.
Participants in the study will be randomized to one of two treatment groups, receiving either oxandrolone (low-dose androgen) or placebo, for two years. All participants will be evaluated for safety at the beginning of the study and at 3, 6, 12, 18, and 24 months. Also at the beginning of the study and every 3 to 6 months thereafter (for a total of 6 visits), the researchers will perform a careful history and physical examination and a bone age X-ray, and obtain a blood sample.
Participation in the trial will last two years and includes 6 clinic visits.
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 |
|---|---|---|
| Oxandrolone | Active comparator | Drug: androgen oxandroloneAndrogen oxandrolone: Oxandrolone, 0.6 > mg/kg/day, orally, for 2 years. |
| Placebo | Placebo comparator | Other: placeboAn inactive substance. |
Who may qualify
- Ages
- 4 to 12 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Karyotype diagnosis of Klinefelter syndrome
- Chronological age of 4-12 years
- No treatment with androgen in the past year
Key exclusion criteria (3 listed)
- Major liver, kidney or other systemic disease
- Variant karyotypes including 47,XYY males
- Evidence of spontaneous onset of puberty, defined as testicular size > 4ml
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 |
|---|---|---|
| androgen oxandroloneOxandrolone ,06 >mg/kg/day, orally, for 2 years | Drug | Oxandrolone |
| placeboan inactive substance | Other | Placebo |
Primary outcome
Motor Function/Strength
Time frame: 2 years per subject
Outcome measures were tested using the following assessments: Bruininks-Osertesky Test of Motor Proficiency (BOT) subscales of (1) Visual Motor Control, (2) Upper limb Speed, and (3) Strength, Physical and Neurological Evaluation for Soft Signs (PANESS), and Hand Strength Dynamometer. BOT assess the child's motor development and includes standard scores (mean=100, SD=15) and subtest scores and is normed for sex and age (4-14.5 years). PANESS assesses the time required to press thumb to 4 fingers 20 times for the dominant and nondominant hands and includes standard scores (mean=100, SD=15) with age-specific norms (4-18 years). Hand strength dynamometer assess hand strength in the dominant and nondominant hands and includes standard scores (mean=100, SD=15). Data is expressed as standard scores with mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scorers imply better function.
4 secondary outcomes
Cognitive Function and Language
Time frame: 2 years per subject
Working Memory/Attention
Time frame: 2 years per participant
Psychosocial and Behavior Domain
Time frame: 2 years per participants
Psychosocial and Behavior Domain
Time frame: 2 years per subject
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29931143Davis SM, Lahlou N, Cox-Martin M, Kowal K, Zeitler PS, Ross JL. Oxandrolone Treatment Results in an Increased Risk of Gonadarche in Prepubertal Boys With Klinefelter Syndrome. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3449-3455. doi: 10.1210/jc.2018-00682.
- Derived from this study: PubMed 28285751Ross JL, Kushner H, Kowal K, Bardsley M, Davis S, Reiss AL, Tartaglia N, Roeltgen D. Androgen Treatment Effects on Motor Function, Cognition, and Behavior in Boys with Klinefelter Syndrome. J Pediatr. 2017 Jun;185:193-199.e4. doi: 10.1016/j.jpeds.2017.02.036. Epub 2017 Mar 10.
- Derived from this study: PubMed 27637014Davis S, Lahlou N, Bardsley M, Temple MC, Kowal K, Pyle L, Zeitler P, Ross J. Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome. Andrology. 2016 Nov;4(6):1169-1177. doi: 10.1111/andr.12275. Epub 2016 Sep 16.
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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.
Judith L. Ross, M.D. principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing androgen oxandrolone in people with Klinefelter Syndrome, run by Thomas Jefferson University 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 3 inclusion and 3 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 8 Jul 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jul 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?
Motor Function/Strength (time frame: 2 years per subject). 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 NCT00348946, which also lists 3 linked publications.
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 8 Jul 2021.