- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02072759
Acetylcarnitine and Metabolic Flexibility
Preservation of Metabolic Flexibility by Acetylcarnitine Formation
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Limburg
-
Maastricht, Limburg, Netherlands, 6229 ER
- Maastricht University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 40-70 years
- Overweight/obese, BMI 25-35 kg/m2
- Stable dietary habits
- Generally healthy with no medication use that interferes with metabolism
Exclusion Criteria:
- Fasting plasma glucose >7.1 mmol/l
- Haemoglobin <7.8 mmol/l
- Hypertension: blood pressure > 140 mmHg systolic or 90 mmHg diastolic
- Cardiac problems, such as angina pectoris, cardiac infarction and arrhythmias
- Plasma creatinine concentration higher than 115 micromol/l (in men) en 100 micromol (in women).
- Any medical condition requiring treatment and/or medication that interferes with investigated parameters
- Unstable body weight (weight gain or loss > 3 kg in the past three months)
- Participation in another biomedical study within 1 month prior to the screening visit
- Subjects with contra-indication for MRI
- Subjects, who do not want to be informed about unexpected medical findings, or do not wish that their treating physician is informed, cannot participate in the study.
- Subject are not allowed to donate blood three months prior to the start of the study and three months after finishing the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Carnitine supplement
|
Carnitine supplement (oral ingestion with meals) Total dosage of 2g carnitine per day for 36 days.
|
PLACEBO_COMPARATOR: Placebo
Placebo supplement
|
|
NO_INTERVENTION: Healthy control
Healthy control group
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
metabolic flexibility
Time Frame: 36 days
|
delta RER between basal and insulin-stimulated state)
|
36 days
|
Insulin sensitivity
Time Frame: 36 days
|
36 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
exercise-induced acetylcarnitine concentrations
Time Frame: 36 days
|
36 days
|
|
meal-induced acetylcarnitine formation
Time Frame: 36 days
|
36 days
|
|
CrAT activity
Time Frame: 36 days
|
determined in muscle biopsy samples
|
36 days
|
fasted blood plasma levels of FFA, triglycerides and glucose and post-meal area under the curve (AUC)
Time Frame: 36 days
|
36 days
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximal aerobic capacity (VO2max)
Time Frame: screening
|
screening
|
Body composition (DEXA)
Time Frame: screening
|
screening
|
Glucose tolerance (OGTT)
Time Frame: screening
|
screening
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Vera B Schrauwen, PhD, Maastricht University Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NL44572.068.13
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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