Markers of Carnitine Acetyltransferase (CrAT) Protein Activity and Carnitine Availability

Searching for Non-invasive Magnetic Resonance-based Markers for CrAT Protein Activity and Carnitine Availability in Skeletal Muscle

This study aims to measure skeletal muscle metabolism in vivo during exercise using the non-invasive Magnetic Resonance Spectroscopy (MRS) technique. Specifically, phosphocreatine (PCr) kinetic and Acetylcarnitine levels will be determined at resting, during exercise and during the recovery post exercise. The target population is adult healthy men, with a wide range of maximal physical capacity.

Study Overview

• Status: Completed
• Conditions: Metabolic Disturbance; Metabolism and Nutrition Disorder
• Intervention / Treatment: Other: Exercise metabolism

Detailed Description

Skeletal muscle mitochondrial activation during the transition from resting metabolism to exercise may modulated by CrAT activity. Furthermore, dynamic changes in acetylcarnitine during the transition from exercise to resting metabolism (acetylcarnitine off-kinetic) may also reflect the action of CrAT protein. To date, the only possibility to get information on CrAT activity is by taking a muscle biopsy and perform enzyme activity assays ex vivo. By dynamic MRS scanning, it might be possible to deduce information that reflects CrAT activity, thereby making the biopsy sampling unnecessary.

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

In this study, 13 healthy young males (BMI <25 kg/m2), aged 18-40yr with different maximal aerobic capacity will be included. Specifically, 4 volunteers with a VO2max <40 ml/kg/min, 5 volunteers with a VO2max between 41 and 50 ml/kg/min and 4 volunteers with a VO2max >50 ml/kg/min will be included.

Description

Inclusion Criteria:

• Males, Generally healthy
• Age 18-40 years old
• BMI 18 - 25 kg/m2
• No medication use that interfere with the aims of the study
• Stable level of daily physical activity or training for at least 6 months

Exclusion Criteria:

• Females
• Regular smokers, drug abuse
• Participation in other studies
• Weight gain/loss > 3 kg in the last 6 months
• Contraindications for MRS scans:
• Vegetarian eating behavior

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CrAT subjects; 13 healthy adult men, with a wide range of maximal aerobic capacity will be included. Subjects will be classified as trained, physical active and untrained according to their VO2max. Subject will perform one-legged knee extension and flexion exercise inside the MRS scanner and cycling outside the scanner	Other: Exercise metabolism; Participants will perform a series of exercises inside and outside the MRS/MRI scanner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle PCr on-kinetic during exercise and carnitine acetyltransferase (CrAT) protein content/activity	The correlation between skeletal muscle PCr on-kinetic during one-legged exercise and CrAT protein activity will be determined.	MRS+Exercise test day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle acetylcarnitine recovery after one-legged exercise and carnitine acetyltransferase (CrAT) protein content/activity	The correlation between skeletal muscle acetylcarnitine off-kinetic after one-legged exercise and CrAT protein activity will be determined.	MRS+Exercise test day 2
Skeletal muscle CrAT protein activity, from muscle biopsy, and PCr breakdown rate during one-legged exercise	The correlation between CrAT protein activity and PCr hydrolysis/breakdown will be determined	MRS+Exercise test day 1
Skeletal muscle acetylcarnitine formation capacity upon exercise and total carnitine availability in skeletal muscle	The correlation between acetylcarnitine formation upon exercise and total carnitine availability will be determined	MRS+Exercise test day 2
Skeletal muscle mitochondrial function in vitro	The association between Skeletal muscle mitochondrial function in vitro and in vivo	MRS+Exercise test day 2
Skeletal muscle oxygen availability	in vivo assessment of oxygen availability in muscle tissue upon hypoxic stimulus during resting	MRS test day 1

Collaborators and Investigators

• Sponsor: Maastricht University
• Investigators: Principal Investigator: Vera Schrauwen-Hinderling, PhD, Maastricht University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 12, 2019
• Primary Completion (ACTUAL): February 1, 2020
• Study Completion (ACTUAL): February 1, 2020

Study Registration Dates

• First Submitted: October 3, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (ACTUAL): October 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Acetylcarnitine kinetic; Phosphocreatine (PCr) kinetic
• Additional Relevant MeSH Terms: Nutrition Disorders
• Other Study ID Numbers: NL63005.068.18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No