Clinical trial NCT03697928: Markers of Carnitine Acetyltransferase (CrAT) Protein Activity and Carnitine Availability
Official title: Searching for Non-invasive Magnetic Resonance-based Markers for CrAT Protein Activity and Carnitine Availability in Skeletal Muscle
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metabolism and Nutrition Disorder
Metabolic Disturbance
Keywords: Acetylcarnitine kinetic
Phosphocreatine (PCr) kinetic
Lead sponsor: Maastricht University
Sponsor class: OTHER
First posted: 2018-10-05
Enrollment: 13
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Skeletal muscle PCr on-kinetic during exercise and carnitine acetyltransferase (CrAT) protein content/activity
timeFrame: MRS+Exercise test day 2
Secondary outcomes:
measure: Skeletal muscle acetylcarnitine recovery after one-legged exercise and carnitine acetyltransferase (CrAT) protein content/activity
timeFrame: MRS+Exercise test day 2
measure: Skeletal muscle CrAT protein activity, from muscle biopsy, and PCr breakdown rate during one-legged exercise
timeFrame: MRS+Exercise test day 1
measure: Skeletal muscle acetylcarnitine formation capacity upon exercise and total carnitine availability in skeletal muscle
timeFrame: MRS+Exercise test day 2
measure: Skeletal muscle mitochondrial function in vitro
timeFrame: MRS+Exercise test day 2
measure: Skeletal muscle oxygen availability
timeFrame: MRS test day 1
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
Study officials:
affiliation: Maastricht University
name: Vera Schrauwen-Hinderling, Phd
role: PRINCIPAL_INVESTIGATOR
References: