AdrenomyeloneuropathyPhase 2NCT01495260
A Clinical Trial for AMN: Validation of Biomarkers of Oxidative Stress, Efficacy and Safety of a Mixture of Antioxidants
A Phase 2 study testing N-acetylcysteine, lipoic acid and vitamin E in people with Adrenomyeloneuropathy, run by Pujol, Aurora, M.D. at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Adrenomyeloneuropathy
- What is being tested?
- N-acetylcysteine, lipoic acid and vitamin E
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteSpain
- Study dates
- Sep 2011to Nov 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
About this study
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
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
- Being tested
- N-acetylcysteine, lipoic acid, vitamin E
- Keywords
- XALD, AMN
- Medical subject headings
- Adrenoleukodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
N-acetylcysteine, 800-2400 mg daily for 2 months
lipoic acidDrug
lipoic acid, 300-600 mg daily for 2 months
vitamin EDrug
vitamin E, 150-300 mg daily for 2 months
| Study group | Role | What they receive |
|---|---|---|
| N-acetylcysteine, lipoic acid and vitamin E | Experimental | Two Dose titration design Receives: Drug: N-acetylcysteine; Drug: lipoic acid; Drug: vitamin E |
What is being measured
The primary outcome is the main question the study is designed to answer.
oxidative lesion biomarkers
oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers
Measured: 12 months
Secondary outcomes (1)
clinical parameters
spasticity, disability,electroneurograms and evocated potentials. Cranial and spinal NMR will be done at the beginning and the end of the trial.
Measured: 2, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2011 (estimated)
- Study startSep 2011
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AdrenomyeloneuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pujol, Aurora, M.D.
- Collaborators
- Ministerio de Sanidad, Servicios Sociales e Igualdad, Fundacion Hesperia
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01495260
- Sponsor's protocol ID
- XAMNANTIOXAP2010
- Status last verified
- Sep 2016
- First submitted
- 28 Nov 2011
- Last updated
- 11 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 21786300Galino 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.
PubMed 21453200Parameswaran 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.
PubMed 35778568Casasnovas 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.
PubMed 31077039
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01495260
- Acronym / sponsor ID
- XAMNANTIOXAP2010
- Conditions
- Adrenomyeloneuropathy
- Keywords
- XALD, AMN
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Pujol, Aurora, M.D.
- Collaborators
- Ministerio de Sanidad, Servicios Sociales e Igualdad, Fundacion Hesperia
- Study start
- Sep 2011
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 19 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| N-acetylcysteine, lipoic acid and vitamin E | Experimental | Drug: N-acetylcysteine, Drug: lipoic acid, Drug: vitamin ETwo Dose titration design |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineN-acetylcysteine, 800-2400 mg daily for 2 months | Drug | N-acetylcysteine, lipoic acid and vitamin E |
| lipoic acidlipoic acid, 300-600 mg daily for 2 months | Drug | N-acetylcysteine, lipoic acid and vitamin E |
| vitamin Evitamin E, 150-300 mg daily for 2 months | Drug | N-acetylcysteine, lipoic acid and vitamin E |
Primary outcome
oxidative lesion biomarkers
Time frame: 12 months
oxidative lesion biomarkers: protein, DNA and peroxidation biomarkers
1 secondary outcome
clinical parameters
Time frame: 2, 6 and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2019.
- Background: PubMed 21786300Lopez-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.
- Background: PubMed 21453200Galino 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.
- Derived from this study: PubMed 35778568Parameswaran 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.
- Derived from this study: PubMed 31077039Casasnovas 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.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-acetylcysteine, lipoic acid and vitamin E in people with Adrenomyeloneuropathy, run by Pujol, Aurora, M.D. at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
oxidative lesion biomarkers (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01495260, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2019; AzTrials last refreshed its copy on 8 Nov 2026.