Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Androgen Effect on Klinefelter Syndrome Motor Outcome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00348946
Recruitment Status : Completed
First Posted : July 6, 2006
Results First Posted : July 8, 2021
Last Update Posted : July 8, 2021
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Thomas Jefferson University

Brief 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.

Condition or disease Intervention/treatment Phase
Klinefelter Syndrome Drug: androgen oxandrolone Other: placebo Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 93 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Androgen Effect on Motor/Cognitive Outcome in Klinefelter Syndrome
Study Start Date : July 2006
Actual Primary Completion Date : November 30, 2017
Actual Study Completion Date : November 30, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Oxandrolone

Arm Intervention/treatment
Active Comparator: Oxandrolone
Androgen oxandrolone: Oxandrolone, 0.6 > mg/kg/day, orally, for 2 years.
Drug: androgen oxandrolone
Oxandrolone ,06 >mg/kg/day, orally, for 2 years

Placebo Comparator: Placebo
An inactive substance.
Other: placebo
an inactive substance




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Cognitive Function and Language [ Time Frame: 2 years per subject ]
    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.

  2. Working Memory/Attention [ Time Frame: 2 years per participant ]
    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.

  3. Psychosocial and Behavior Domain [ Time Frame: 2 years per participants ]
    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.

  4. Psychosocial and Behavior Domain [ Time Frame: 2 years per subject ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   4 Years to 12 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Karyotype diagnosis of Klinefelter syndrome
  • Chronological age of 4-12 years
  • No treatment with androgen in the past year

Exclusion Criteria:

  • Major liver, kidney or other systemic disease
  • Variant karyotypes including 47,XYY males
  • Evidence of spontaneous onset of puberty, defined as testicular size > 4ml

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00348946


Locations
Layout table for location information
United States, Pennsylvania
Thomas Jefferson University, Department of Pediatrics, 1025 Walnut Street, Suite 726
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Thomas Jefferson University
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Judith L. Ross, M.D. Thomas Jefferson University
  Study Documents (Full-Text)

Documents provided by Thomas Jefferson University:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00348946    
Other Study ID Numbers: R01NS050597-01A2 ( U.S. NIH Grant/Contract )
First Posted: July 6, 2006    Key Record Dates
Results First Posted: July 8, 2021
Last Update Posted: July 8, 2021
Last Verified: July 2021
Keywords provided by Thomas Jefferson University:
Klinefelter syndrome
androgen
androgen oxandrolone
Additional relevant MeSH terms:
Layout table for MeSH terms
Klinefelter Syndrome
Syndrome
Disease
Pathologic Processes
Sex Chromosome Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Gonadal Disorders
Endocrine System Diseases
Hypogonadism
Androgens
Oxandrolone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anabolic Agents