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

Metabolic Disturbance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03697928
• Other study ID #: NL63005.068.18
• Status: Completed
• Start date: March 12, 2019
• Est. completion date: February 1, 2020

Study information

• Verified date: October 2020
• Source: Maastricht University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: February 1, 2020
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Metabolic Disturbance
• Metabolism and Nutrition Disorder
• Nutrition Disorders

Intervention

Other:
• Exercise metabolism
Participants will perform a series of exercises inside and outside the MRS/MRI scanner.

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Skeletal muscle mitochondrial function in vitro	The association between Skeletal muscle mitochondrial function in vitro and in vivo	MRS+Exercise test day 2
Secondary	Skeletal muscle oxygen availability	in vivo assessment of oxygen availability in muscle tissue upon hypoxic stimulus during resting	MRS test day 1