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

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).

Study Overview

• Status: Completed
• Conditions: Adrenomyeloneuropathy; X-linked Adrenoleukodystrophy
• Intervention / Treatment: Drug: Bezafibrate

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Bezalip retard.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Side effects	At 4, 8, 12, 16, 20 and 24 weeks.
Cholesterol (total-, HDL, and LDL-cholesterol) in plasma.	24 weeks

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: The Stop ALD Foundation
• Investigators: Principal Investigator: Bwee Tien Poll - The, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: July 13, 2010
• First Submitted That Met QC Criteria: July 16, 2010
• First Posted (Estimate): July 19, 2010

Study Record Updates

• Last Update Posted (Estimate): August 10, 2011
• Last Update Submitted That Met QC Criteria: August 9, 2011
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: AMN; X-ALD; adrenomyeloneuropathy phenotype
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Leukoencephalopathies; Adrenal Gland Diseases; Hereditary Central Nervous System Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Adrenoleukodystrophy; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Bezafibrate
• Other Study ID Numbers: MEC 09/278