Clinical trial NCT00348946: Androgen Effect on Klinefelter Syndrome Motor Outcome
Official title: Androgen Effect on Motor/Cognitive Outcome in Klinefelter Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Klinefelter Syndrome
Keywords: Klinefelter syndrome
androgen
androgen oxandrolone
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2006-07-06
Enrollment: 93
Sex: MALE
Minimum age (years): 4
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Motor Function/Strength
timeFrame: 2 years per subject
Secondary outcomes:
measure: Cognitive Function and Language
timeFrame: 2 years per subject
measure: Working Memory/Attention
timeFrame: 2 years per participant
measure: Psychosocial and Behavior Domain
timeFrame: 2 years per participants
measure: Psychosocial and Behavior Domain
timeFrame: 2 years per subject
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Department of Pediatrics, 1025 Walnut Street, Suite 726
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Judith L. Ross, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.