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

Overview

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).

Full Title of Study: “Effect of Bezafibrate on Very Long Chain Fatty Acid Metabolism in Men With X-linked Adrenoleukodystrophy (X-ALD)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 2011

Interventions

  • Drug: Bezafibrate
    • Week 0 to 12: 400 mg once daily 1 tablet. Week 13 to 24: 400 mg once daily 2 tablets.

Arms, Groups and Cohorts

  • 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.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Academisch Medisch Centrum – Universiteit van Amsterdam (AMC-UvA)
  • Collaborator
    • The Stop ALD Foundation
  • Provider of Information About this Clinical Study
    • Department of (pediatric) neurology, Academisch Medisch Centrum, Amsterdam, The Netherlands
  • Overall Official(s)
    • Bwee Tien Poll – The, MD, PhD, Principal Investigator, Academisch Medisch Centrum – Universiteit van Amsterdam (AMC-UvA)

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