Cardiometabolic Profiles of Boys With Klinefelter Syndrome

Completed

• Conditions: Sex Chromosome Aneuploidy; XXY Syndrome; Klinefelter Syndrome; 47,XXY
• Interventions: Other: No intervention

• Registration Number: NCT02723305
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study First Submitted: 2016-03-24
• Study First Submitted QC: 2016-03-24
• Study First Posted: 2016-03-30
• Study Start: 2016-05
• Primary Completion: 2017-12
• Study Completion: 2017-12
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-04
• Last Update Posted: 2022-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 31

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Testosterone Naive	No intervention	Boys with Klinefelter syndrome age 12-17 who are Tanner 3, 4, or 5. No exogenous testosterone exposure in the past 5 years
Testosterone exposed	No intervention	Boys with Klinefelter syndrome age 12-17 who are Tanner 3, 4, or 5. +topical testosterone treatment for \>1 year

Primary Outcome Measures

Name	Time	Method
VO2 peak	baseline	The primary outcome will be peak oxygen consumption (VO2 peak) during exercise on a bicycle ergometer

Secondary Outcome Measures

Name	Time	Method
Body composition	baseline	Percent body fat by dual-energy x-ray absorptiometry
Muscle mitochondrial metabolism	baseline	Rate of mitochondrial phosphorylation by 31-phosphorus magnetic resonance spectroscopy of the calf muscles
Insulin sensitivity	baseline	oral disposition index with Glucola
Liver fat	baseline	Intrahepatic fat by abdominal magnetic resonance imaging

Trial Locations

Locations (1)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States