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

Study Overview
=================
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.

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

Conditions
-----------------
Adrenomyeloneuropathy

Intervention / Treatment
-----------------
* Drug: N-acetylcysteine
* Drug: lipoic acid
* Drug: vitamin E


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetylcysteine, lipoic acid and vitamin E<br>Two Dose titration design | Drug: N-acetylcysteine<br>* N-acetylcysteine, 800-2400 mg daily for 2 months<br>Drug: lipoic acid<br>* lipoic acid, 300-600 mg daily for 2 months<br>Drug: vitamin E<br>* vitamin E, 150-300 mg daily for 2 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| oxidative lesion biomarkers | oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
XALD, AMN