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

Sponsor

Maastricht University (Other)

Overall Status

Completed

CT.gov ID

NCT03697928

Collaborator

(none)

Enrollment

Location

10.7

Actual Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metabolism and Nutrition Disorder Metabolic Disturbance	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 Design

Study Type:

Observational

Actual Enrollment :

13 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

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

Actual Study Start Date :

Mar 12, 2019

Actual Primary Completion Date :

Feb 1, 2020

Actual Study Completion Date :

Feb 1, 2020

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maastricht University	Maastricht	Limburg	Netherlands

Sponsors and Collaborators

Maastricht University

Investigators

Principal Investigator: Vera Schrauwen-Hinderling, Phd, Maastricht University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Maastricht University

ClinicalTrials.gov Identifier:

NCT03697928

Other Study ID Numbers:

NL63005.068.18

First Posted:

Oct 5, 2018

Last Update Posted:

Oct 19, 2020

Last Verified:

Oct 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Maastricht University

Acetylcarnitine kinetic

Phosphocreatine (PCr) kinetic

Additional relevant MeSH terms:

Nutrition Disorders

Study Results

No Results Posted as of Oct 19, 2020