A Clinical Trial for AMN: Validation of Biomarkers of Oxidative Stress, Efficacy and Safety of a Mixture of Antioxidants
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Adrenomyeloneuropathy |
Drug: N-acetylcysteine Drug: lipoic acid Drug: vitamin E |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- oxidative lesion biomarkers [ Time Frame: 12 months ] [ Designated as safety issue: No ]oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers
- clinical parameters [ Time Frame: 2, 6 and 12 months ] [ Designated as safety issue: No ]spasticity, disability,electroneurograms and evocated potentials. Cranial and spinal NMR will be done at the beginning and the end of the trial.
| Estimated Enrollment: | 20 |
| Study Start Date: | September 2011 |
| Estimated Study Completion Date: | November 2013 |
| Estimated Primary Completion Date: | November 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: N-acetylcysteine, lipoic acid and vitamin E
Two Dose titration design
|
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
|
Eligibility| Ages Eligible for Study: | 18 Years to 64 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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,
- advanced 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.
Contacts and Locations| Contact: Aurora Pujol, MD PhD | +34 932607342 | apujol@idibell.cat |
| Contact: Montse Ruiz, PhD | +34932607500 ext 3332 | mruiz@idibell.cat |
| Spain | |
| Hospital Universitari de Bellvitge | Recruiting |
| L'Hospitalet de LLobregat, Barcelona, Spain, 08907 | |
| Principal Investigator: Carlos Casasnovas, MD PhD | |
More Information
Additional Information:
Publications:
| Responsible Party: | Onofre, Aurora Pujol, M.D. |
| ClinicalTrials.gov Identifier: | NCT01495260 History of Changes |
| Other Study ID Numbers: | XAMNANTIOXAP2010 |
| Study First Received: | November 28, 2011 |
| Last Updated: | May 8, 2012 |
| Health Authority: | Spain: Agencia Española de Medicamentos y Productos Sanitarios |
Keywords provided by Onofre, Aurora Pujol, M.D.:
|
XALD AMN |
Additional relevant MeSH terms:
|
Adrenoleukodystrophy Hereditary Central Nervous System Demyelinating Diseases Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Peroxisomal Disorders Leukoencephalopathies Demyelinating Diseases Mental Retardation, X-Linked Mental Retardation Neurobehavioral Manifestations Neurologic Manifestations Genetic Diseases, X-Linked |
Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Metabolism, Inborn Errors Metabolic Diseases Adrenal Insufficiency Adrenal Gland Diseases Endocrine System Diseases Acetylcysteine N-monoacetylcystine Antioxidants Thioctic Acid Vitamin E Alpha-Tocopherol Tocopherols Tocotrienols |
ClinicalTrials.gov processed this record on May 23, 2013