A Clinical Trial for AMN: Validation of Biomarkers of Oxidative Stress, Efficacy and Safety of a Mixture of Antioxidants

Adrenomyeloneuropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01495260
• Other study ID #: XAMNANTIOXAP2010
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: November 2013

Study information

• Verified date: September 2016
• Source: Onofre, Aurora Pujol, M.D.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adrenoleukodystrophy
• Adrenomyeloneuropathy

Intervention

Drug:
• N-acetylcysteine
N-acetylcysteine, 800-2400 mg daily for 2 months
• lipoic acid
lipoic acid, 300-600 mg daily for 2 months
• vitamin E
vitamin E, 150-300 mg daily for 2 months

Locations

Country	Name	City	State
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de LLobregat	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Onofre, Aurora Pujol, M.D.	Fundacion Hesperia, Ministerio de Sanidad, Servicios Sociales e Igualdad

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Galino J, Ruiz M, Fourcade S, Schlüter A, López-Erauskin J, Guilera C, Jove M, Naudi A, García-Arumí 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. — View Citation

López-Erauskin J, Fourcade S, Galino J, Ruiz M, Schlüter 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	oxidative lesion biomarkers	oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers	12 months
Secondary	clinical parameters	spasticity, disability,electroneurograms and evocated potentials. Cranial and spinal NMR will be done at the beginning and the end of the trial.	2, 6 and 12 months

External Links

•   Link
•   Link
•   The Neurometabolic Diseases Lab, led by ICREA Research Professor Aurora Pujol, is integrated in the Neurosciences Area of IDIBELL.