Clinical trial NCT02723305: Cardiometabolic Profiles of Boys With Klinefelter Syndrome
Official title: Cardiometabolic Profiles of Pubertal Boys With Klinefelter Syndrome With or Without One Year of Exogenous Testosterone Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Klinefelter Syndrome
47,XXY
Sex Chromosome Aneuploidy
XXY Syndrome
Keywords: Klinefelter syndrome
XXY
Sex chromosome aneuploidy
sex chromosome variation
hypogonadism
cardiometabolic
body composition
exercise capacity
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2016-03-30
Enrollment: 31
Sex: MALE
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will enroll 10 youth with 47,XXY who will be subdivided into 2 groups:

1. Testosterone naïve (no exogenous testosterone within the past 5 years)
2. Testosterone exposed (topical testosterone treatment for at least 1 year but no more than 2 years) Most subjects will be recruited at the completion of a monitored, double-blind randomized controlled trial ongoing at our institution. Additional subjects may be recruited to meet enrollment goals.

Brief summary: This study plans to learn more about how to measure the way the the body's energy system works in boys with Klinefelter syndrome, including the heart, lungs, muscles, and liver. This is important to know so that investigators understand how hormones and an extra X chromosome relate to diseases such as diabetes, extra weight gain, heart disease and liver diseases.

Detailed description: Klinefelter syndrome (KS) is the most common chromosomal abnormality in males and is associated with primary gonadal failure in adolescence and a high morbidity and mortality from cardiovascular-related diseases (CVD) in adulthood. Recent studies in children and adolescent boys with KS have found a high prevalence of CVD risk markers, however the underlying mechanisms have not been explored. Our central hypothesis is that pubertal boys with KS have relative testosterone deficiency resulting in abnormal energy metabolism that predisposes them to later CVD, and that exogenous testosterone will modify these abnormalities.

In this study, investigators will measure markers of cardiometabolic risk in pubertal boys with KS.

Eligibility criteria: Inclusion Criteria:

* Male, 47,XXY karyotype (non-mosaic)
* Age 12-17 years
* Tanner stage 3-5 pubic hair
* T naïve group only: No exogenous androgen exposure within the past 5 years
* T exposed group only: currently on topical testosterone, with duration of treatment between 1-2 years.

Exclusion Criteria:

* Cognitive, psychiatric, or physical impairment resulting in inability to tolerate the study procedures
* MRI incompatible metal
* Diagnosis of type 1 or type 2 diabetes
* Hypertension greater than 140/90 mm/Hg at rest (would make exercise studies unsafe)
* Weight \> 300 lbs (limit for DEXA)
* Testosterone treatment for \<1 year or \>2 years

Primary outcomes:
measure: VO2 peak
timeFrame: baseline
Secondary outcomes:
measure: Body composition
timeFrame: baseline
measure: Liver fat
timeFrame: baseline
measure: Muscle mitochondrial metabolism
timeFrame: baseline
measure: Insulin sensitivity
timeFrame: baseline
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado/Children's Hospital Colorado
name: Shanlee M Davis, 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.