Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oxandrolone | Active Comparator | Androgen oxandrolone: Oxandrolone, 0.6 > mg/kg/day, orally, for 2 years. |
|
| Placebo | Placebo Comparator | An inactive substance. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| androgen oxandrolone | Drug | Oxandrolone ,06 >mg/kg/day, orally, for 2 years |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 2 years per subject |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Judith L. Ross, M.D. | Thomas Jefferson University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Thomas Jefferson University, Department of Pediatrics, 1025 Walnut Street, Suite 726 | Philadelphia | Pennsylvania | 19107 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29931143 | Derived | 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. | |
| 28285751 | Derived | Ross 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Oxandrolone | androgen oxandrolone: Oxandrolone ,0.6 >mg/kg/day, orally, for 2 years. |
| FG001 | Placebo | placebo: an inactive substance |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Oxandrolone | androgen oxandrolone: Oxandrolone ,0.6 >mg/kg/day, orally, for 2 years. |
| BG001 | Placebo | placebo: an inactive substance |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Some participants were not able to complete all test and/or it was determined by the investigator that their results do reflect their ability and they were removed from the analysis. | Posted | Mean | Standard Deviation | score on a scale | 2 years per subject |
Two years
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oxandrolone | androgen oxandrolone: Oxandrolone ,0.6 >mg/kg/day, orally, for 2 years |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Musculoskeletal complaints | Musculoskeletal and connective tissue disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Judith L. Ross, M.D. | Thomas Jefferson University | 215-955-1648 | judith.ross@jefferson.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 1, 2011 | May 4, 2021 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D007713 | Klinefelter Syndrome |
| ID | Term |
|---|---|
| D058533 | Sex Chromosome Disorders of Sex Development |
| D012734 | Disorders of Sex Development |
| D014564 | Urogenital Abnormalities |
| D052776 | Female Urogenital Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| placebo |
| Other |
an inactive substance |
|
| 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. | 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. | 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. | 2 years per subject |
| 27637014 | Derived | Davis 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Tanner 1 pubic hair | Count of Participants | Participants |
|
| BMI Standard Deviation Score (SDS) | Mean | Standard Deviation | kg/m^2 |
|
| Waist circumference percentile >75 percentile | Count of Participants | Participants |
|
| Total cholesterol | Mean | Standard Deviation | mg/dL |
|
| LDL cholesterol | Mean | Standard Deviation | mg/dL |
|
| Triglycerides | Mean | Standard Deviation | mg/dL |
|
| Triglycerides > 100 mg/dL | Count of Participants | Participants |
|
| HDL cholesterol | Mean | Standard Deviation | mg/dL |
|
| HDL cholesterol < 50 mg/dL | Count of Participants | Participants |
|
| Fasting blood glucose, mg/dL | Mean | Standard Deviation | mg/dL |
|
| Fasting blood glucose > 110 mg/dL | Count of Participants | Participants |
|
| Systolic blood pressure | Mean | Standard Deviation | mm Hg |
|
| Systolic blood pressure > 90th percentile for age and height | Count of Participants | Participants |
|
| Diastolic blood pressure | Mean | Standard Deviation | mm Hg |
|
| Diastolic blood pressure > 90th percentile for age and height | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Oxandrolone | androgen oxandrolone: Oxandrolone ,06 >mg/kg/day, orally, for 2 years |
| OG001 | Placebo | placebo: an inactive substance |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 2 years per subject |
|
|
|
|
| Secondary | 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. | Some participants were not able to complete all assessments and/or it was determined by the investigator that their results do reflect their ability and they were removed from the analysis . | Posted | Mean | Standard Deviation | score on a scale | 2 years per participant |
|
|
|
|
| Secondary | 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. | Some participants were not able to complete all assessments and/or it was determined by the investigator that their results do reflect their ability and they were removed from the analysis. | Posted | Mean | Standard Deviation | score on a scale | 2 years per participants |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | 2 years per subject |
|
|
|
|
| 0 |
| 46 |
| 0 |
| 46 |
| 36 |
| 46 |
| EG001 | Placebo | placebo: an inactive substance | 0 | 47 | 0 | 47 | 38 | 47 |
| Infections (any) | Infections and infestations | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Emergency room visits - Musculoskeletal | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Emergency room visits - Asthma/allergy | Immune system disorders | Systematic Assessment |
|
| Emergency room visits - Gastrointestinal | Gastrointestinal disorders | Systematic Assessment |
|
| Emergency room visits | Nervous system disorders | Systematic Assessment |
|
| Emergency room visits | Infections and infestations | Systematic Assessment |
|
| Emergency room visits - other | General disorders | Systematic Assessment |
|
| Hospitalizations - Medical | General disorders | Systematic Assessment |
|
| Hospitalizations - Psychiatric | Psychiatric disorders | Systematic Assessment |
|
Not provided
Not provided
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D025064 | Sex Chromosome Disorders |
| D025063 | Chromosome Disorders |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D007006 | Hypogonadism |
| DAS: Nonverbal Cluster |
|
| DAS: Spatial Cluster |
|
| 0.57 |
| Superiority |
| DAS: Nonverbal Cluster | ANCOVA | 0.55 | Superiority |
| DAS: Spatial Cluster | ANCOVA | 0.65 | Superiority |
| Phonemic fluency |
|
|
| Semantic fluency |
|
|
| CPT: omissions |
|
|
| CPT: commissions |
|
|
| CPT: hit reaction time |
|
|
| CPT variability |
|
|
| CPT: preservations |
|
|
| 0.36 |
| Superiority |
| Semantic fluency | ANCOVA | 0.37 | Superiority |
| CPT: omissions | ANCOVA | 0.41 | Superiority |
| CPT: commissions | ANCOVA | 0.73 | Superiority |
| CPT: hit reaction time | ANCOVA | 0.40 | Superiority |
| CPT: variability | ANCOVA | 0.95 | Superiority |
| CPT: preservations | ANCOVA | 0.78 | Superiority |
| CBCL: internalizing total t-score |
|
|
| CBCL: externalizing total t-score |
|
|
| CDI: total t-score |
|
|
| 0.10 |
| Superiority |
| CBCL: externalizing total | ANCOVA | 0.24 | Superiority |
| CDI: Total | ANCOVA | 0.50 | Superiority |