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

NCT01165060 | Completed

• 1 other identifier: MEC 09/278
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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).

Conditions

X-linked Adrenoleukodystrophy; Adrenomyeloneuropathy

Keywords

X-ALD; AMN; adrenomyeloneuropathy phenotype

Outcome Measures

Primary Outcomes (1)

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

  24 weeks

Secondary Outcomes (2)

• Side effects

  At 4, 8, 12, 16, 20 and 24 weeks.

• Cholesterol (total-, HDL, and LDL-cholesterol) in plasma.

  24 weeks

Study Arms (1)

Bezafibrate

EXPERIMENTAL

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

Interventions

Bezafibrate DRUG

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

Also known as: Bezalip retard.

Bezafibrate

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• The Stop ALD Foundation: collaborator

Study Sites (1)

Academisch Medisch Centrum

Amsterdam, North Holland, 1100 DD, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 22911730 DERIVED

MeSH Terms

Conditions

Adrenoleukodystrophy

Interventions

Bezafibrate

Condition Hierarchy (Ancestors)

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; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzoates; Acids, Carbocyclic; Chlorobenzoates; Phenyl Ethers; Ethers; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Bwee Tien Poll - The, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 13, 2010
• First Posted: July 19, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: August 10, 2011

Record last verified: 2010-07

Locations

NL (1)