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

Onofre, Aurora Pujol, M.D.

Status and phase: Completed; Phase 2

Conditions: Adrenomyeloneuropathy

Treatments: Drug: N-acetylcysteine; Drug: vitamin E; Drug: lipoic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT01495260

XAMNANTIOXAP2010

Details and patient eligibility

About

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.

Enrollment: 13 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 1 patient group

N-acetylcysteine, lipoic acid and vitamin E

Experimental group

Description:

Two Dose titration design

Treatment:

Drug: lipoic acid

Drug: N-acetylcysteine

Drug: vitamin E