The Effect of Bezafibrate on the Level of Very Long Chain Fatty Acids (VLCFA) in X-linked Adrenoleukodystrophy (X-ALD) (BEZA)
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.
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.
Adult men with X-linked adrenoleukodystrophy.
Intervention (if applicable):
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).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Bezafibrate on Very Long Chain Fatty Acid Metabolism in Men With X-linked Adrenoleukodystrophy (X-ALD)|
- Very long chain fatty acids (VLCFA; C22:0, C24:0 and C26:0) in plasma, lymphocytes and erythrocytes. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Side effects [ Time Frame: At 4, 8, 12, 16, 20 and 24 weeks. ] [ Designated as safety issue: Yes ]
- Cholesterol (total-, HDL, and LDL-cholesterol) in plasma. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||July 2010|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
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.
Week 0 to 12: 400 mg once daily 1 tablet. Week 13 to 24: 400 mg once daily 2 tablets.
Other Name: Bezalip retard.
|Academisch Medisch Centrum|
|Amsterdam, NH, Netherlands, 1100 DD|
|Principal Investigator:||Bwee Tien Poll - The, MD, PhD||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|