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Acetylcarnitine and Metabolic Flexibility

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02072759
First Posted: February 27, 2014
Last Update Posted: July 14, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
European Foundation for the Study of Diabetes
Information provided by (Responsible Party):
Maastricht University Medical Center
  Purpose
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.

Condition Intervention
Glucose Intolerance Dietary Supplement: Carnitine supplement Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Preservation of Metabolic Flexibility by Acetylcarnitine Formation

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • metabolic flexibility [ Time Frame: 36 days ]
    delta RER between basal and insulin-stimulated state)

  • Insulin sensitivity [ Time Frame: 36 days ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • Maximal aerobic capacity (VO2max) [ Time Frame: screening ]
  • Body composition (DEXA) [ Time Frame: screening ]
  • Glucose tolerance (OGTT) [ Time Frame: screening ]

Enrollment: 24
Study Start Date: March 2014
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carnitine supplement
Carnitine supplement
Dietary Supplement: Carnitine supplement

Carnitine supplement (oral ingestion with meals)

Total dosage of 2g carnitine per day for 36 days.

  • 1 carnitine supplement at breakfast (500mg)
  • 1 carnitine supplement at lunch (500mg)
  • 2 carnitine supplements at diner (2x 500mg=1000mg)
Placebo Comparator: Placebo
Placebo supplement
Dietary Supplement: Placebo
No Intervention: Healthy control
Healthy control group

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.

  Eligibility

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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

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


Locations
Netherlands
Maastricht University Medical Center
Maastricht, Limburg, Netherlands, 6229 ER
Sponsors and Collaborators
Maastricht University Medical Center
European Foundation for the Study of Diabetes
Investigators
Principal Investigator: Vera B Schrauwen, PhD Maastricht University Medical Center
  More Information

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT02072759     History of Changes
Other Study ID Numbers: NL44572.068.13
First Submitted: February 25, 2014
First Posted: February 27, 2014
Last Update Posted: July 14, 2016
Last Verified: June 2015

Keywords provided by Maastricht University Medical Center:
Insulin sensitivity
Metabolic flexibility

Additional relevant MeSH terms:
Glucose Intolerance
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Acetylcarnitine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Nootropic Agents