Ignite Creation Date:
2025-12-24 @ 2:46 PM
Ignite Modification Date:
2026-03-01 @ 4:13 PM
Study NCT ID:
NCT02072759
Status:
COMPLETED
Last Update Posted:
2016-07-14
First Post:
2014-02-25
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Acetylcarnitine and Metabolic Flexibility
Sponsor:
Maastricht University Medical Center
Organization:
Study Overview
Official Title:
Preservation of Metabolic Flexibility by Acetylcarnitine Formation
Status:
COMPLETED
Status Verified Date:
2015-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 a low carnitine availability may limit acetylcarnitine formation, thereby reducing metabolic flexibility. We propose to test the hypothesis that metabolic inflexibility in pre-diabetic subjects and diabetic patients is due to a reduced capacity to form acetylcarnitines.
Detailed Description:
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: