Abstract Details

Title Bezafibrate Does Not Improve Fat Oxidation in Patients with Disorders of Fat Metabolism; a Double Blind, Randomized Clinical Trial

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) S05 - (-)

Poster/Presentation
Number 006

Objective

Background Carnitine palmitoyltransferase (CPT) II and very long-chain acyl-CoAdehydrogenase (VLCAD) deficiencies are the two most common causes of rhabdomyolysis due to fatty acid oxydation impairement in adults. Bezafibrate up-regulate enzyme activities of both enzymes in patients with defects in CPT II and VLCAD, when assessed in vitro, and increased quality of life scores in an uncontrolled study in six CPT II patients. In CPT II and VLCAD deficiencies, fatty acid oxidation (FAO) is normal at rest, but residual enzyme activity is insufficient to increase FAO during exercise. We hypothesized that Bezafibrate would increase FAO and lower perceived exertion during exercise in patients with CPT II and VLCAD deficiencies.

Design/Methods We studied the effect of Bezafibrate/placebo on total FAO by indirect calorimetry and palmitate turnover using stable isotope methodology during cycling exercise in 10 patients with recurrent episodes of rhabdomyolysis caused by CPT II (n=5) and VLCAD (n=5) deficiencies. The study design was 3-month, randomized, double-blind, cross-over (EudraCT: 2008-006704-27). Primary endpoints were FAO and heart rate during exercise.

Results Bezafibrate lowered LDL, triglyceride and free fatty acid concentrations, but palmitate oxidation and total FAO at rest and during exercise, as well as activity levels scored by Bouchard questionnaires, were not changed by Bezafibrate.

Conclusions 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, do not translate into clinically meaningful effects in vivo.

Authors/Disclosures
John Vissing, MD (Rigshospitalet) PRESENTER	Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Solid Biosciences. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AskBio. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Italfarmaco. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Biopharma. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Johnson & Johnson (Janssen). Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Edgewise Therapeutics. The institution of Prof. Vissing has received research support from Rigshospitalet. The institution of Prof. Vissing has received research support from UCB Pharma. The institution of Prof. Vissing has received research support from Sanofi. The institution of Prof. Vissing has received research support from Roche. The institution of Prof. Vissing has received research support from AnJii.
Pascal Laforet (Hopital Pitie Salpetriere)	No disclosure on file
	No disclosure on file
	No disclosure on file
Nicolai Preisler	No disclosure on file
Jayant N. Acharya, MD, DM, FAAN (Southern Illinois University School of Medicine)	Dr. Acharya has nothing to disclose.
	No disclosure on file

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