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

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

Mette Cathrine Ørngreen  1 , Karen Lindhardt Madsen, Nicolai Preisler, Grete Andersen, John Vissing, Pascal Laforêt
Affiliations
Randomized Controlled Trial

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

Mette Cathrine Ørngreen et al. Neurology. .

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.

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Figures

Figure 1
Figure 1. Flow diagram for the bezafibrate study
Figure 2
Figure 2. Fat metabolism
(A) Plasma palmitate concentration, (B) plasma free fatty acid (FFA) concentration, (C) palmitate oxidation, and (D) total fatty acid oxidation (FAO) at rest (gray) and during exercise at 50% to 60% of maximal oxygen uptake capacity (V̇o2max) (black) without and with bezafibrate (green) in 10 patients with carnitine palmitoyltransferase II (n = 5) and very long-chain acyl-CoA dehydrogenase (n = 5) deficiencies. Values are mean ± standard error (SE). *p < 0.05 rest vs exercise; §p < 0.05 placebo vs bezafibrate. Dotted line indicates the mean fatty acid/palmitate oxidation at the 40th minute of exercise in 7 healthy controls exercising at 50% to 60% of V̇o2max, and the shaded area is ±SE.
Figure 3
Figure 3. Exercise capacity
Perceived exertion (Borg) (A) and heart rate (B) during and at the end of exercise at 50% to 60% of maximal oxygen uptake capacity with placebo (closed circle) and bezafibrate (open circle) in 10 patients with carnitine palmitoyltransferase II (n = 5) and very long-chain acyl-CoA dehydrogenase (n = 5) deficiencies. Values are mean ± standard error.
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References

    1. Orngreen MC, Duno M, Ejstrup R, et al. Fuel utilization in subjects with carnitine palmitoyltransferase 2 gene mutations. Ann Neurol 2005;57:60–66 - PubMed
    1. Orngreen MC, Norgaard MG, Sacchetti M, van Engelen BG, Vissing J. Fuel utilization in patients with very long-chain acyl-CoA dehydrogenase deficiency. Ann Neurol 2004;56:279–283 - PubMed
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