Clinical trial NCT01585831: Study of Psychological and Motor Effects of Testosterone in Adolescents With XXY/Klinefelter Syndrome
Official title: Psychological and Motor Effects of Testosterone Therapy in Adolescents With XXY/Klinefelter Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Klinefelter Syndrome
XXY Syndrome
Keywords: Klinefelter syndrome
XXY syndrome
Sex Chromosome Abnormality
Testosterone replacement therapy
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Colorado Clinical & Translational Sciences Institute
name: Children's Hospital Colorado
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2012-04-26
Enrollment: 48
Sex: MALE
Minimum age (years): 8
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline on the Delis-Kaplan Executive Function System
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
measure: Change From Baseline on the Bruininks-Oseretsky Test of Motor Development - 2
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
measure: Change From Baseline on the Conners Parent Rating Scales: DSM Attention
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
measure: Change From Baseline on the Conners Parent Rating Scales: DSM Hyperactivity
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
measure: Change From Baseline on the Conners Parent Rating Scales: Anxiety
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
measure: Change From Baseline on the Conners Parent Rating Scales: Social Skills
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
measure: Change From Baseline on the Conners Parent Rating Scales: Emotional Lability
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
Secondary outcomes:
measure: Change From Baseline on the Vineland Adaptive Behavior Scales - 2nd Edition
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
measure: Change From Baseline on the Wechsler Intelligence Scale for Children - Fourth Edition
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
measure: Change From Baseline on the Comprehensive Test of Phonological Processing
timeFrame: Visit 1 (baseline) and Visit 5 (1 year)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado School of Medicine
name: Nicole Tartaglia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.