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

Phase 2

Completed

• Conditions: Adrenomyeloneuropathy
• Interventions: Drug: N-acetylcysteine; Drug: lipoic acid; Drug: vitamin E

• Registration Number: NCT01495260
• Lead Sponsor: Pujol, Aurora, M.D.

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2011-11-28
• Study First Submitted QC: 2011-12-16
• Study First Posted: 2011-12-19
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Status Verified: 2016-09
• Last Update Submitted: 2019-03-07
• Last Update Posted: 2019-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
N-acetylcysteine, lipoic acid and vitamin E	lipoic acid	Two Dose titration design
N-acetylcysteine, lipoic acid and vitamin E	vitamin E	Two Dose titration design
N-acetylcysteine, lipoic acid and vitamin E	N-acetylcysteine	Two Dose titration design

Primary Outcome Measures

Name	Time	Method
oxidative lesion biomarkers	12 months	oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers

Secondary Outcome Measures

Name	Time	Method
clinical parameters	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.

Trial Locations

Locations (1)

Hospital Universitari de Bellvitge; 🇪🇸 L'Hospitalet de LLobregat, Barcelona, Spain