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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Klinefelter Syndrome
• Intervention / Treatment: Drug: Fenofibrate 145 mg

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado - Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Shanlee M Davis, MD, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2022
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): August 30, 2025

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 11, 2022

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: XXY; Klinefelters; 47, XXY; Klinefelter's Syndrome; Klinefelter
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Chromosome Disorders; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Hypogonadism; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Klinefelter Syndrome; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Fenofibrate
• Other Study ID Numbers: 21-2860

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No