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

This study has been completed.
Sponsor:
Collaborators:
Ministerio de Sanidad, Servicios Sociales e Igualdad
Fundacion Hesperia
Information provided by (Responsible Party):
Onofre, Aurora Pujol, M.D.
ClinicalTrials.gov Identifier:
NCT01495260
First received: November 28, 2011
Last updated: March 19, 2014
Last verified: May 2012
  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

Resource links provided by NLM:


Further study details as provided by Onofre, Aurora Pujol, M.D.:

Primary Outcome Measures:
  • oxidative lesion biomarkers [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers


Secondary Outcome Measures:
  • 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
Study Completion Date: November 2013
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
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,
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495260

Locations
Spain
Hospital Universitari de Bellvitge
L'Hospitalet de LLobregat, Barcelona, Spain, 08907
Sponsors and Collaborators
Onofre, Aurora Pujol, M.D.
Ministerio de Sanidad, Servicios Sociales e Igualdad
Fundacion Hesperia
  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: March 19, 2014
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
Adrenal Gland Diseases
Adrenal Insufficiency
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Endocrine System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hereditary Central Nervous System Demyelinating Diseases
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Leukoencephalopathies
Mental Retardation, X-Linked
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Peroxisomal Disorders
Acetylcysteine
Alpha-Tocopherol
Antioxidants
N-monoacetylcystine
Thioctic Acid
Tocopherols
Tocotrienols
Vitamin E

ClinicalTrials.gov processed this record on October 23, 2014