The Effect of Bezafibrate on the Level of Very Long Chain Fatty Acids (VLCFA) in X-linked Adrenoleukodystrophy (X-ALD) (BEZA)

The Effect of Bezafibrate on the Level of Very Long Chain Fatty Acids (VLCFA) in X-linked Adrenoleukodystrophy (X-ALD)

Effect of Bezafibrate on Very Long Chain Fatty Acid Metabolism in Men With X-linked Adrenoleukodystrophy (X-ALD)

X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder characterised by accumulation of very long chain fatty acids (VLCFA) in plasma and tissue. Presumably this accumulation is responsible for tissue damage. The disease can cause severe demyelinisation of the central nervous system usually causing death in childhood or progressive ambulatory problems in adults caused by a progressive myelopathy. For the latter category of patients no curative treatment is currently available. Recent investigations in human fibroblasts and mice identified bezafibrate as an agent that might reduce VLCFA in patients with X-ALD. Objective of the study: The trial is designed as an open-label pilot study. The main goal is to investigate if bezafibrate can reduce VLCFA in vivo in patient with X-ALD. If there is indeed a biochemical effect, a large follow-up study will be initiated with clinical outcome parameters. Study design: 10 men with X-ALD will use bezafibrate during a period of 6 months (in combination with a low fat diet). On 6 different time points the participants will undergo a venipuncture for detecting possible side effects and to determine the biochemical outcome parameters. Study population: Adult men with X-linked adrenoleukodystrophy. Intervention (if applicable): Bezafibrate. Primary study parameters/outcome of the study: The primary outcome parameters are cholesterol levels (total-, LDL, and HDL) and levels of triglycerides in plasma, VLCFA levels in plasma, leukocytes and erythrocytes and also C26:0-lyso-PC in bloodspots. Secondary study parameters/outcome of the study (if applicable): Secondary outcome parameters are side-effects (subjective and abnormalities in the safety lab).

All patients in the trial will use bezafibrate 400 mg once daily until week 12, and subsequently use 800 mg onde daily until week 24.

Inclusion Criteria: an age of 18 years or older capable of giving informed consent and capable of visiting the hospital for follow-up visits no contra-indications for the use of bezafibrate, e.g. kidney- and/or liver disease. confirmed X-ALD, AMN phenotype (confirmed by VLCFA analysis or analysis of the ABCD1 gene) Exclusion Criteria: use of medication that lowers cholesterol and/or triglycerides (e.g. statins) liver disease or and increase in serum CK of more than 3 times the baseline level treatment with Lorenzo's oil in the 8 weeks preceding the trial

Engelen M, Tran L, Ofman R, Brennecke J, Moser AB, Dijkstra IM, Wanders RJ, Poll-The BT, Kemp S. Bezafibrate for X-linked adrenoleukodystrophy. PLoS One. 2012;7(7):e41013. doi: 10.1371/journal.pone.0041013. Epub 2012 Jul 20.