Clinical Trial: Fat and Sugar Metabolism During Exercise, With and Without L-carnitine in Patients With Carnitine Transporter Deficiency

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Fat and Carbohydrate Metabolism During Exercise, With and Without L-carnitine Supplementation in Patients With Carnitine Transporter Deficiency

Brief Summary:

The investigators wish to investigate fat and sugar metabolism during exercise with and without L-carnitine supplementation in patients with carnitine transporter deficiency (CTD).

Patients with CTD have low plasma- and muscle concentrations of carnitine, which is believed to lead to an impaired fat oxidation. Presently there is no cure available for these patients, but daily intake of L-carnitine has been shown to limit the amount of symptoms. Little is known about the metabolism during exercise and the pathophysiological mechanisms causing the symptoms.

Studying the fat and sugar metabolism in CTD patients will contribute to the understanding of the role of the carnitine transporter in the development of symptoms in these patients. Furthermore, knowledge about the fat and sugar metabolism in these patients can increase the understanding of the role of the carnitine transporter in the metabolism healthy persons.

The investigators have included 8 patients with genetically verified CTD in the study and a group of 10 age- and sex-matched controls. Subjects will perform a 1h cycling test, exercising at a moderate intensity. By measuring the expiration of carbon dioxide (CO2) and consumption of oxygen (O2), the investigators can determine the total fatty acid and carbohydrate oxidation during cycling. At the same time the investigators will measure the patients' whole body palmitate (fat) and glucose (sugar) oxidation rates using stable isotope technique.

The patient group will repeat the cycling test after 4 days without taking their usual L-carnitine treatment. During the treatment break, patients will be admitted to be continuously monitored for heart rhythm disturbances, which is a known but rarely occurring complication to

Detailed Summary:

8 Patients with verified CTD have been included

  • All patients have performed an incremental load exercise test to exhaustion on a cycle ergometer to determine maximal oxygen comsumption rate (VO2 max)
  • One-hour exercise test: Measurement of the total fat and sugar oxidation rates during exercise using stable isotope tracers.

Subjects arrive at the laboratory after 3-9 hours fasting. One IV-catheter is inserted in the cubital vein in one arm and another in a peripheral vein in the other hand. The stable isotope tracers will be given in the cubital vein as a constant infusion of solutions of:

  • [U-13C]-palmitate (0.0026 mg x kg-1 x min-1, after a priming bolus of 0.085 mg x kg-1 NaH13CO3)
  • [1,1,2,3,3-2H5]-glycerol (0.0049 mg x kg-1 x min-1 )
  • [6.6-2H2]-glucose (0.0728 mg x kg-1 x min-1 ) 5 days before the study, subjects must avoid eating food containing corn. Corn contains larger amounts of C13, which we use as a tracer, and can therefore disturb the measurements.

For two hours the subjects rest while receiving the infusions until the tracers have distributed in the body and reached a steady state. After the rest, the subjects exercise on the cycle-ergometer until exhaustion or for a maximum of 1 hour at an intensity that corresponds to 60-70% of VO2max.

Every other minute during exercise, the heart rate is recorded and the subject evaluates his/her degree of exertion (Rate of Perceived Exertion, RPE) on a Borg scale.

Blood and breath samples:

Sponsor: Karen Lindhardt Madsen

Current Primary Outcome: The whole body palmitate and carbohydrate oxidation rate in CTD patients during exercise [ Time Frame: With and without L-carnitine treatment ]

The whole body palmitate and carbohydrate oxidation will be assessed during 1h exercise test performed on a cycle-ergometer using stable isotope technique combined with indirect calorimetry.


Original Primary Outcome: Same as current

Current Secondary Outcome: The maximal oxidative capacity (VO2max) as an indicator of exercise tolerance and performance in CTD patients [ Time Frame: During a 15 min incremental intensity exercise test and during a 1h moderate intensity cycling test ]

Original Secondary Outcome: Same as current

Information By: Rigshospitalet, Denmark

Dates:
Date Received: August 5, 2013
Date Started: August 2013
Date Completion:
Last Updated: May 4, 2015
Last Verified: May 2015