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

NCT01495260 | Completed Phase 2

• 1 other identifier: XAMNANTIOXAP2010
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Adrenomyeloneuropathy

Keywords

XALD; AMN

Outcome Measures

Primary Outcomes (1)

• oxidative lesion biomarkers

  oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers

  12 months

Secondary Outcomes (1)

• clinical parameters

  2, 6 and 12 months

Study Arms (1)

N-acetylcysteine, lipoic acid and vitamin E

EXPERIMENTAL

Two Dose titration design

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

Interventions

N-acetylcysteine DRUG

N-acetylcysteine, 800-2400 mg daily for 2 months

N-acetylcysteine, lipoic acid and vitamin E

lipoic acid DRUG

lipoic acid, 300-600 mg daily for 2 months

N-acetylcysteine, lipoic acid and vitamin E

vitamin E DRUG

vitamin E, 150-300 mg daily for 2 months

N-acetylcysteine, lipoic acid and vitamin E

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Symptomatic AMN patients,
• years old,
• male and female,
• clinically and biochemically diagnosed;
• females must be obligated heterozygotes or must have gene mutation identified.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pujol, Aurora, M.D.: lead
• Ministerio de Sanidad, Servicios Sociales e Igualdad: collaborator
• Fundacion Hesperia: collaborator

Study Sites (1)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Related Publications (4)

• Lopez-Erauskin J, Fourcade S, Galino J, Ruiz M, Schluter 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.

  PMID: 21786300 BACKGROUND

• Galino J, Ruiz M, Fourcade S, Schluter A, Lopez-Erauskin J, Guilera C, Jove M, Naudi A, Garcia-Arumi 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.

  PMID: 21453200 BACKGROUND

• Parameswaran J, Goicoechea L, Planas-Serra L, Pastor A, Ruiz M, Calingasan NY, Guilera C, Aso E, Boada J, Pamplona R, Portero-Otin M, de la Torre R, Ferrer I, Casasnovas C, Pujol A, Fourcade S. Activating cannabinoid receptor 2 preserves axonal health through GSK-3beta/NRF2 axis in adrenoleukodystrophy. Acta Neuropathol. 2022 Aug;144(2):241-258. doi: 10.1007/s00401-022-02451-2. Epub 2022 Jul 1.

  PMID: 35778568 DERIVED

• Casasnovas C, Ruiz M, Schluter A, Naudi A, Fourcade S, Veciana M, Castaner S, Alberti A, Bargallo N, Johnson M, Raymond GV, Fatemi A, Moser AB, Villarroya F, Portero-Otin M, Artuch R, Pamplona R, Pujol A. Biomarker Identification, Safety, and Efficacy of High-Dose Antioxidants for Adrenomyeloneuropathy: a Phase II Pilot Study. Neurotherapeutics. 2019 Oct;16(4):1167-1182. doi: 10.1007/s13311-019-00735-2.

  PMID: 31077039 DERIVED

Related Links

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

MeSH Terms

Conditions

Adrenoleukodystrophy

Interventions

Acetylcysteine; Thioctic Acid; Vitamin E

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Carboxylic Acids; Thiophenes; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2011
• First Posted: December 19, 2011
• Study Start: September 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: March 11, 2019

Record last verified: 2016-09

Locations

ES (1)