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

Sponsor

University of Colorado, Denver (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05498090

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

35.9

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Klinefelter Syndrome	Drug: Fenofibrate 145 mg	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

2 arms in study: cross-sectional (cases v. controls); interventional (cases only: pre and post fenofibrate intervention)2 arms in study: cross-sectional (cases v. controls); interventional (cases only: pre and post fenofibrate intervention)

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Aug 30, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

No Intervention: Arm 1 (Cross-sectional, Cases v. Controls)

Cases (those with Klinefelter) vs. controls (those without Klinefelter)

Experimental: Arm 2 (Interventional with cases)

Cases (those with Klinefelter); Comparison of outcomes pre and post fenofibrate intervention, 145mg PO daily for 4 weeks

Drug: Fenofibrate 145 mg

Fenofibrate 145 mg PO daily for 4 weeks

Outcome Measures

Primary Outcome Measures

maximal rate of fat oxidation [1 month]
maximal rate of fat oxidation during prolong submaximal exercise
skeletal muscle fat oxidation [1 month]
Maximal skeletal muscle mitochondrial respiration with lipid substrate

Secondary Outcome Measures

differentially-expressed genes in plasma [1 month]
Expression levels of UCP2, PLTP, CRAT, ECH1, SLC27A1, SLC27A4, CPT1B from fasting blood draw
differentially-expressed genes in skeletal muscle tissue [1 month]
Expression levels of UCP2, PLTP, CRAT, ECH1, SLC27A1, SLC27A4, CPT1B from skeletal muscle biopsy

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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