Bezafibrate in skeletal muscle fatty acid oxidation disorders: a randomized clinical trial

Neurology. 2014 Feb 18;82(7):607-13. doi: 10.1212/WNL.0000000000000118. Epub 2014 Jan 22.

Abstract

Objective: To assess whether bezafibrate increases fatty acid oxidation (FAO) and lowers heart rate (HR) during exercise in patients with carnitine palmitoyltransferase (CPT) II and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies.

Methods: This was a 3-month, randomized, double-blind, crossover study of bezafibrate in patients with CPT II (n = 5) and VLCAD (n = 5) deficiencies. Primary outcome measures were changes in FAO, measured with stable-isotope methodology and indirect calorimetry, and changes in HR during exercise.

Results: Bezafibrate lowered low-density lipoprotein, triglyceride, and free fatty acid concentrations; however, there were no changes in palmitate oxidation, FAO, or HR during exercise.

Conclusion: Bezafibrate does not improve clinical symptoms or FAO during exercise in patients with CPT II and VLCAD deficiencies. These findings indicate that previous in vitro studies suggesting a therapeutic potential for fibrates in disorders of FAO do not translate into clinically meaningful effects in vivo.

Classification of evidence: This study provides Class I evidence that bezafibrate 200 mg 3 times daily is ineffective in improving changes in FAO and HR during exercise in adults with CPT II and VLCAD deficiencies.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / blood
  • Acyl-CoA Dehydrogenase, Long-Chain / deficiency*
  • Acyl-CoA Dehydrogenase, Long-Chain / metabolism
  • Adolescent
  • Adult
  • Aged
  • Bezafibrate / administration & dosage
  • Bezafibrate / blood
  • Bezafibrate / pharmacology*
  • Carnitine O-Palmitoyltransferase / deficiency*
  • Clinical Protocols
  • Congenital Bone Marrow Failure Syndromes
  • Cross-Over Studies
  • Fatty Acids / blood
  • Fatty Acids / metabolism*
  • Female
  • Humans
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / blood
  • Hypolipidemic Agents / pharmacology*
  • Lipid Metabolism, Inborn Errors / blood
  • Lipid Metabolism, Inborn Errors / diagnosis
  • Lipid Metabolism, Inborn Errors / drug therapy*
  • Lipid Metabolism, Inborn Errors / metabolism*
  • Male
  • Middle Aged
  • Mitochondrial Diseases / blood
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscular Diseases / blood
  • Muscular Diseases / diagnosis
  • Muscular Diseases / drug therapy*
  • Muscular Diseases / metabolism*
  • Treatment Outcome
  • Young Adult

Substances

  • Fatty Acids
  • Hypolipidemic Agents
  • Acyl-CoA Dehydrogenase, Long-Chain
  • Carnitine O-Palmitoyltransferase
  • Bezafibrate

Supplementary concepts

  • Carnitine Palmitoyltransferase II Deficiency, Late-Onset
  • VLCAD deficiency