Acetylcarnitine and Metabolic Flexibility
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|ClinicalTrials.gov Identifier: NCT02072759|
Recruitment Status : Completed
First Posted : February 27, 2014
Last Update Posted : July 14, 2016
|Condition or disease||Intervention/treatment||Phase|
|Glucose Intolerance||Dietary Supplement: Carnitine supplement Dietary Supplement: Placebo||Not Applicable|
Background: Insulin resistant subjects and type 2 diabetic patients are characterized by a decreased metabolic flexibility: a reduced capability to switch from fat oxidation in the basal state to carbohydrate oxidation in the insulin-stimulated state. This metabolic inflexibility is an early hallmark in the development of diabetes. Recent evidence suggests that low carnitine availability may limit acetylcarnitine formation, thereby reducing metabolic flexibility.
Objectives: We will investigate whether subjects with impaired glucose tolerance (IGT) show a diminished capacity to form acetylcarnitine in the face of high substrate availability. Therefore, we will use a novel non-invasive 1H-Magnetic Resonance Spectroscopy (1H-MRS) protocol to determine in vivo, and in time, the formation of acetylcarnitine in skeletal muscle. Additionally, we will examine whether carnitine supplementation increases the capacity to form acetylcarnitine and improves metabolic flexibility and insulin sensitivity in IGT subjects.
Study design: 12 subjects with IGT will be included and will be subjected to either placebo- or carnitine treatment (daily capsules with 2g of L-carnitine or placebo) in a randomized, placebo-controlled, double blind crossover design. After both interventions, acetylcarnitine formation after a mixed meal will be determined by 1H-MRS and meal-induced changes in fat and glucose oxidation by indirect calorimetry. The maximal acetylcarnitine formation will be measured after a cycling test via 1H-MRS. A hyperinsulinemic-euglycemic clamp will be performed to determine insulin sensitivity. Biopsies will be taken to measure free carnitine and carnitine acetyltransferase (CrAT) activity. To investigate whether differences in acetylcarnitine formation may be involved in variations in glucose tolerance, twelve control subjects, matched for BMI and age but glucose tolerant (based on oral glucose tolerance test, according to WHO criteria) will also be included and will undergo all measurements once without any intervention.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Preservation of Metabolic Flexibility by Acetylcarnitine Formation|
|Study Start Date :||March 2014|
|Actual Primary Completion Date :||June 2016|
|Actual Study Completion Date :||June 2016|
Experimental: Carnitine supplement
Dietary Supplement: Carnitine supplement
Carnitine supplement (oral ingestion with meals)
Total dosage of 2g carnitine per day for 36 days.
Placebo Comparator: Placebo
Dietary Supplement: Placebo
No Intervention: Healthy control
Healthy control group
- metabolic flexibility [ Time Frame: 36 days ]delta RER between basal and insulin-stimulated state)
- Insulin sensitivity [ Time Frame: 36 days ]
- exercise-induced acetylcarnitine concentrations [ Time Frame: 36 days ]
- meal-induced acetylcarnitine formation [ Time Frame: 36 days ]
- CrAT activity [ Time Frame: 36 days ]determined in muscle biopsy samples
- fasted blood plasma levels of FFA, triglycerides and glucose and post-meal area under the curve (AUC) [ Time Frame: 36 days ]
- Maximal aerobic capacity (VO2max) [ Time Frame: screening ]
- Body composition (DEXA) [ Time Frame: screening ]
- Glucose tolerance (OGTT) [ Time Frame: screening ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02072759
|Maastricht University Medical Center|
|Maastricht, Limburg, Netherlands, 6229 ER|
|Principal Investigator:||Vera B Schrauwen, PhD||Maastricht University Medical Center|