Interrogating Fatty Acid Metabolism Impairment and Clinical Correlates in Males With Klinefelter Syndrome

Study Overview
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Brief Summary
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This study will learn more about how the body uses energy. Usually, the body uses sugars as energy first and then fats are used when the sugar stores are gone. Some people have trouble using fats as energy. This can lead to feeling tired, difficulty exercising, and storing too much fat where it does not belong (like in the muscle). It is believed that some boys and men with Klinefelter Syndrome may not be able to use fats as energy normally, and that a medication called fenofibrate could help this.

Official Title
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Interrogating Fatty Acid Metabolism Impairment and Clinical Correlates in Males With Klinefelter Syndrome

Conditions
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Klinefelter Syndrome

Intervention / Treatment
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* Drug: Fenofibrate 145 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Ages 15 to 40 years Total testosterone concentration within the normal range for age and pubertal stage For the KS group only: genetic testing results confirming KS Exclusion Criteria: Liver disease (ALT or AST > 3x upper limit of normal) Renal impairment (estimated creatinine clearance <80 ml/min) Diabetes mellitus (A1c > 6.4%) Untreated hypogonadism Treatment with a PPAR agonist (including fish oil) or statin within the past month Unstable medications with any medication added or removed within the past 2 weeks or plan for medication changes during the study period Inability to tolerate study procedures, including any medical conditions that make exercise unsafe at the discretion of the study physician For the KS group only: known allergy to fibrates, inability to swallow tablets

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 arms in study: cross-sectional (cases v. controls); interventional (cases only: pre and post fenofibrate intervention)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm 1 (Cross-sectional, Cases v. Controls)<br>Cases (those with Klinefelter) vs. controls (those without Klinefelter) | |
| Experimental: Arm 2 (Interventional with cases)<br>Cases (those with Klinefelter); Comparison of outcomes pre and post fenofibrate intervention, 145mg PO daily for 4 weeks | Drug: Fenofibrate 145 mg<br>* Fenofibrate 145 mg PO daily for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximal rate of fat oxidation | maximal rate of fat oxidation during prolong submaximal exercise | 1 month | 
| skeletal muscle fat oxidation | Maximal skeletal muscle mitochondrial respiration with lipid substrate | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| differentially-expressed genes in plasma | Expression levels of UCP2, PLTP, CRAT, ECH1, SLC27A1, SLC27A4, CPT1B from fasting blood draw | 1 month | 
| differentially-expressed genes in skeletal muscle tissue | Expression levels of UCP2, PLTP, CRAT, ECH1, SLC27A1, SLC27A4, CPT1B from skeletal muscle biopsy | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Klinefelters, XXY, 47, XXY, Klinefelter's Syndrome, Klinefelter