Clinical Trial: Effect of Bezafibrate on Muscle Metabolism in Patients With Fatty Acid Oxidation Defects

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

Official Title: Evaluation of the Effect of Bezafibrate on Muscle Metabolism During Exercise in Patients With CPTII and VLCAD Deficiency

Brief Summary: The investigators propose to evaluate the effect of bezafibrate on metabolism during exercise in 22 adult patients affected with carnitine palmitoyltransferase II (CPTII) or very-long chain acyl-CoA-dehydrogenase (VLCAD) deficiencies. This study will be an 9-month, randomized, double-blind, placebo-controlled crossover trial. The trial will be conducted in two centers: Institut de Myologie, Pitié-Salpêtrière Hospital in France, and Rigshospitalet, University of Copenhagen, in Denmark. The main criteria for assessing the potential effect of this drug will be the fat oxidation rate studied during a moderate workload on cycle ergometer, after infusion of stable isotopes (palmitate and glucose tracers).

Detailed Summary:

Background and research aim:

Carnitine palmitoyltransferase II (CPTII) and very-long chain acyl-CoA-dehydrogenase (VLCAD) deficiencies are the two most common inherited disorders of mitochondrial fatty acid oxidation (FAO) in adults, both inherited in an autosomal recessive manner. Mitochondrial FAO plays a pivotal role for maintaining energy homeostasis in situations such as fasting, fever or prolonged exercise that require both glucose sparing and major energy supply. In these situations, a number of tissues such as skeletal muscle, heart, and liver, favour fatty acids as the main source of energy. Long-chain fatty acids (LCFA), that represent the major part of endogenous free fatty acids cannot enter the mitochondrial matrix compartment by simple diffusion, and the transfer of LCFA across the mitochondrial membranes is governed by a multienzymatic system named carnitine palmitoyltransferase (CPT) consisting of two enzymes: CPT I and II. CPT I, a key regulatory step of LCFA oxidation, is located within the outer mitochondrial membrane, while CPT II is appended to the inner face of the inner mitochondrial membrane. CPTs I and II catalyze a single reaction (carnitine + acyl-CoA ⇔ acylcarnitine + CoA~SH) in the forward and reverse directions, respectively. VLCAD is bound to the inner mitochondrial membrane, and catalyses the first step of the long-chain fatty acid β-oxidation spiral (Izai et al., 1992).

Various phenotypes of CPT II and VLACD deficiencies have been described. Severe neonatal or infantile clinical life-threatening symptoms may occur with hypoketotic hypoglycemia, liver failure, and cardiomyopathy during the first months or years of life (Demaugre et al, 1991; Bonnefont et al, 1996; Vianey-Saban et al. 1998; Andresen et al., 1999). Conversely, the "adult" forms of these diseases are more p
Sponsor: Rigshospitalet, Denmark

Current Primary Outcome: Fatty acid oxidation [ Time Frame: Two years ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Heart rate [ Time Frame: Two years ]

Original Secondary Outcome: Same as current

Information By: Rigshospitalet, Denmark

Dates:
Date Received: September 23, 2009
Date Started: October 2009
Date Completion:
Last Updated: May 29, 2012
Last Verified: May 2012