A Clinical Trial for AMN: Validation of Biomarkers of Oxidative Stress, Efficacy and Safety of a Mixture of Antioxidants
Overview
X-linked adrenoleukodystrophy is a rare, demyelinating and neurodegenerative disorder, due to a loss of function of a fatty acid transporter, the peroxisomal ABCD1protein. Its more frequent phenotype, the adrenomyeloneuropathy in adults, is characterized by axonal degeneration in spinal cord, spastic paraparesis and a disabling peripheral neuropathy. Actually, there is no efficient treatment for the disease. Our work in the last twelve years dissecting the physiopathological basis of the disorder has uncovered an involvement of the oxidative stress early in the neurodegenerative cascade. In a preclinical trial we have identified an antioxidant cocktail that efficiently reverse the clinical symptoms and the axonal degeneration in the mouse model for the disease. We propose the translation of the results to an open trial to test the tolerance and effectiveness of these drugs in the correction of the previously identified oxidative lesion biomarkers, as a first step to a randomized versus placebo, multicentric and international trial. You will be clinically explored and assessed in the Hospital Universitari of Bellvitge (HUB) using clinical scales for spasticity, disability, electroneurogram and cranial and spinal Nuclear Magnetic resonance (NMR). The information will be collected in a data base that will be of great value to improve the present attention and the future follow-up to facilitate your inclusion in therapeutic randomized, double blind, against placebo clinical trials.
Full Title of Study: “A Clinical Trial for Adrenomyeloneuropathy (AMN): Validation of Biomarkers of Oxidative Stress, and Efficacy, Tolerance and Safety of a Mixture of the Antioxidants N-acetylcysteine, Lipoic Acid and Vitamin E”
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: November 2013
Interventions
- Drug: N-acetylcysteine
- N-acetylcysteine, 800-2400 mg daily for 2 months
- Drug: lipoic acid
- lipoic acid, 300-600 mg daily for 2 months
- Drug: vitamin E
- vitamin E, 150-300 mg daily for 2 months
Arms, Groups and Cohorts
- Experimental: N-acetylcysteine, lipoic acid and vitamin E
- Two Dose titration design
Clinical Trial Outcome Measures
Primary Measures
- oxidative lesion biomarkers
- Time Frame: 12 months
- oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers
Secondary Measures
- clinical parameters
- Time Frame: 2, 6 and 12 months
- spasticity, disability,electroneurograms and evocated potentials. Cranial and spinal NMR will be done at the beginning and the end of the trial.
Participating in This Clinical Trial
Inclusion Criteria
- Symptomatic AMN patients, – 18-64 years old, – male and female, – clinically and biochemically diagnosed; – females must be obligated heterozygotes or must have gene mutation identified. Exclusion Criteria:
- Pregnant and lactation in females, – Cerebral inflammatory disease with cognitive disorder, and/or – need the help of two walking sticks, – epilepsy, – hypersensibility to cysteine related compounds, – transaminases 2 fold up normal values.
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: 64 Years
Are Healthy Volunteers Accepted: No
Investigator Details
- Lead Sponsor
- Onofre, Aurora Pujol, M.D.
- Collaborator
- Ministerio de Sanidad, Servicios Sociales e Igualdad
- Provider of Information About this Clinical Study
- Sponsor
References
Lopez-Erauskin J, Fourcade S, Galino J, Ruiz M, Schluter A, Naudi A, Jove M, Portero-Otin M, Pamplona R, Ferrer I, Pujol A. Antioxidants halt axonal degeneration in a mouse model of X-adrenoleukodystrophy. Ann Neurol. 2011 Jul;70(1):84-92. doi: 10.1002/ana.22363.
Galino J, Ruiz M, Fourcade S, Schluter A, Lopez-Erauskin J, Guilera C, Jove M, Naudi A, Garcia-Arumi E, Andreu AL, Starkov AA, Pamplona R, Ferrer I, Portero-Otin M, Pujol A. Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy. Antioxid Redox Signal. 2011 Oct 15;15(8):2095-107. doi: 10.1089/ars.2010.3877. Epub 2011 Jun 8.
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