Cardiometabolic Profiles of Boys With Klinefelter Syndrome

Study Overview
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Brief Summary
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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
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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.

Official Title
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Cardiometabolic Profiles of Pubertal Boys With Klinefelter Syndrome With or Without One Year of Exogenous Testosterone Treatment

Conditions
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47,XXY, Klinefelter Syndrome, Sex Chromosome Aneuploidy, XXY Syndrome

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Testosterone Naive<br>Boys with Klinefelter syndrome age 12-17 who are Tanner 3, 4, or 5. No exogenous testosterone exposure in the past 5 years | Other: No intervention<br> <br> |
| Testosterone exposed<br>Boys with Klinefelter syndrome age 12-17 who are Tanner 3, 4, or 5. +topical testosterone treatment for >1 year | Other: No intervention<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VO2 peak | The primary outcome will be peak oxygen consumption (VO2 peak) during exercise on a bicycle ergometer | baseline | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Klinefelter syndrome, XXY, Sex chromosome aneuploidy, sex chromosome variation, hypogonadism, cardiometabolic, body composition, exercise capacity