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

Study Description

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Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
X-linked Adrenoleukodystrophy; Adrenomyeloneuropathy	Drug: Bezafibrate	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	10 participants
Intervention Model:	Single Group Assignment
Masking:	None (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)
Study Start Date :	July 2010
Actual Primary Completion Date :	August 2011
Actual Study Completion Date :	August 2011

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Bezafibrate; 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.	Drug: Bezafibrate; Week 0 to 12: 400 mg once daily 1 tablet. Week 13 to 24: 400 mg once daily 2 tablets.; Other Name: Bezalip retard.

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Very long chain fatty acids (VLCFA; C22:0, C24:0 and C26:0) in plasma, lymphocytes and erythrocytes. [ Time Frame: 24 weeks ]

Secondary Outcome Measures :

1. Side effects [ Time Frame: At 4, 8, 12, 16, 20 and 24 weeks. ]
2. Cholesterol (total-, HDL, and LDL-cholesterol) in plasma. [ Time Frame: 24 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

Netherlands
Academisch Medisch Centrum
Amsterdam, NH, Netherlands, 1100 DD

Sponsors and Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

The Stop ALD Foundation

Investigators

Principal Investigator:	Bwee Tien Poll - The, MD, PhD	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Department of (pediatric) neurology, Academisch Medisch Centrum, Amsterdam, The Netherlands
ClinicalTrials.gov Identifier:	NCT01165060 History of Changes
Other Study ID Numbers:	MEC 09/278
First Posted:	July 19, 2010
Last Update Posted:	August 10, 2011
Last Verified:	July 2010

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

X-ALD; AMN; adrenomyeloneuropathy phenotype

Additional relevant MeSH terms:

Adrenoleukodystrophy; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked

Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Bezafibrate; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents