AdrenoleukodystrophyMATRIXNCT04925349
Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia
An observational study of Adrenoleukodystrophy and Adrenomyeloneuropathy, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
This study is a national, non-randomized, open-label, multi-site with minimal risk study in adult with adrenomyeloneuropathy (AMN), childhood and adult subjects with cerebral ALD (cALD), juvenile/adult metachromatic leukodystrophy (MLD) and adults with leukoencephalopathy and axonal spheroids and pigmented glia… Read more about this study
- Who is it for?
- Ages 15 months to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Adrenoleukodystrophy, Adrenomyeloneuropathy, Metachromatic Leukodystrophy
- What is being tested?
- Blood sample collection
- How many people
- 100 participants
- Where
- 2 sitesFrance
- Study dates
- 30 Aug 2021to Feb 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 15 months to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Pediatric and adult populations. Both affected (C-CALD, AMN, A-CALD, MLD, ALSP), presymptomatic children carrying ABCD1 mutations (PRE-ALD), presymptomatic patient adults carrying CSF1R mutations (PRE-ALSP) and age-matched control subjects will be enrolled (N=10/group). Minor subjects (C-CALD, MLD, PRE-ALD and controls) will be included, based on childhood onset of C-CALD and MLD
Who may be able to join
- Boys aged between 3 and 18 years (inclusive) diagnosed with C-CALD (elevated levels of VLCFA and leukodystrophy at brain MRI)
- Boys or girls aged between 15 months and 18 years (inclusive) diagnosed with MLD (low ARSA activity and accumulation of sulfatides in urine)
- Presymptomatic boys carrying ABCD1 mutations aged between 3 and 18 years (inclusive) (PRE-ALD)
- Adult males or females aged between 18 and 60 diagnosed with MLD (low ARSA activity and accumulation of sulfatides in urine)
- Males aged between 18 and 60 years diagnosed with AMN (elevated VLCFA and clinical symptoms of AMN without leukodystrophy at brain MRI)
- Males aged between 18 and 60 years diagnosed with CALD (elevated VLCFA with leukodystrophy at brain MRI)
Show all 13Show fewer
- Adult males or females aged between 18 and 60 years diagnosed with ALSP (CSF1R mutation and leukodystrophy at brain MRI)
- Presymptomatic patient adults (males or females) carrying CSF1R mutations (PRE-ALSP)
- Children (15 months-18 years) without neurologic disease (no obvious neurological symptoms, normal neurologic examination)
- Adults aged between 18 and 60 years without neurologic disease (no overt neurological symptoms)
- Informed consent obtained :
- from the parents or guardian for children patients and children controls;
- from subject himself for adult patients and adult controls.
Who cannot join
- Participation to a therapeutic clinical trial
- Treatment likely to modify the immune system
- Unable to have a blood collection (i.e. low hemoglobin level at the investigator's judgment)
- Any other reason, to the discretion of the investigator
- Children or adults without health insurance or social security
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Christelle AUGER contact
France2 sites, 2 recruiting
- Recruiting
AP-HP Hôpital Bicêtre
Le Kremlin-Bicêtre, 94275
Fanny MOCHEL, MD-PhD, +33 1 5727 44 82, fanny.mochel@icm-institut.org
Caroline SEVIN, MD-PhD, +33 1 45 21 30 17, caroline.sevin@inserm.fr
- Recruiting
AP-HP Hôpital La Pitié Salpêtrière
Paris, 75013
About this study
Official title: MATRIX - "Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia"
This study is a national, non-randomized, open-label, multi-site with minimal risk study in adult with adrenomyeloneuropathy (AMN), childhood and adult subjects with cerebral ALD (cALD), juvenile/adult metachromatic leukodystrophy (MLD) and adults with leukoencephalopathy and axonal spheroids and pigmented glia (ALSP). 49 subjects will be enrolled with one blood sample collection during one of their medical follow-up visit.
This trial will evaluate the role of innate immunity to influence disease progression in X-ALD, MLD and ALSP, and if the mutations related to these leukodystrophies result in a specific immune response leading to the pathogenesis.
Read the detailed description
X-linked Adrenoleukodystrophy (X-ALD), Metachromatic Leukodystrophy (MLD) and Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) are among the most frequent inherited leukodystrophies. X-ALD and MLD can affect both children and adults, while it is thought that ALSP onset exclusively during adulthood. These three diseases are characterized by phenotypic variability and poor genotype-phenotype correlation. In childhood forms of MLD and childhood cerebral ALD (C-CALD) a devastating cerebral demyelination and neuronal degeneration lead to a rapid neurologic degradation and premature death. Patients with the adult form of X-ALD (adrenomyeloneuropathy (AMN), 60% of males) display a progressive spastic paraplegia without brain involvement. However, 20% of AMN patients will also develop cerebral ALD. Patients diagnosed with the juvenile/adult (JA-) MLD form are affected by a progressive decline of their cognitive function, followed later by that of the motor abilities. ALSP patients present a rapidly progressive neurodegenerative disorder that impairs behavioural, cognitive and motor functions.
Several arguments support the contribution of the immune response and neuroinflammation in these three leukodystrophies. In X-ALD, activation of microglia (macrophages of the CNS) plays an essential role in the acute demyelination phase, where a severe inflammatory process occurs. In ALSP, the dysfunctional protein (CSF1R) is almost exclusively expressed in microglia. Even if MLD is not considered as a neuroinflammatory disease per se, microglia activation and increased inflammatory cytokines are observed in the brain of MLD patients and mice. Even if the most commonly accepted hypothesis is that neuroinflammation is caused by secondary activation of microglia following phagocytosis of myelin debris full of undegraded material, a primitive role of the inflammation due to macrophages (MAC) dysfunction has emerged in recent years.
MATRIX proposes to explore how disease-related mutations affect key components of MAC activation responses and how it reflects on their functionality.
- Conditions
- Adrenoleukodystrophy, Adrenomyeloneuropathy, Metachromatic Leukodystrophy, Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia
- Being tested
- Blood sample collection
- Keywords
- Leukodystrophy, Central Nervous System Diseases, Nervous System Diseases, Immune system, Neuroinflammation
- Medical subject headings
- Adrenoleukodystrophy, Leukodystrophy, Metachromatic, Hereditary Diffuse Leukoencephalopathy with Spheroids, Central Nervous System Diseases, Nervous System Diseases, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sample collectionDiagnostic test
blood sample collection
| Study group | Role | What they receive |
|---|---|---|
| affected subjects | * adult patients with adrenomyeloneuropathy/adrenoleukodystrophy
* children with adrenoleukodystrophy
* children with metachromatic leukodystrophy Receives: Diagnostic Test: Blood sample collection | |
| control subjects | * healthy children
* heatthy adults Receives: Diagnostic Test: Blood sample collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Macrophages functionality - distribution of monocytes
distribution of monocytes in the CD14-/+/++ and CD16-/+ classification using flow cytometry (% of CD14++/16-; CD14++/16+; CD14+/16+; CD14-/16-)
Measured: 2 years after blood collection
Macrophages functionality - myelin phagocytosis capacity
percentage of myelin high, myelin low and myelin negative cells using flow cytometry
Measured: 2 years after blood collection
Macrophages functionality - HLA levels
maximum fluorescence intensity for HLA markers using flow cytometry
Measured: 2 years after blood collection
Secondary outcomes (2)
Macrophages metabolic profiling
Macrophages metabolic profiling (>2000 metabolites) using liquid chromatography coupled to high resolution mass spectrometry
Measured: 2 years after blood collection
Macrophages transcriptomic profiling
Macrophages transcriptomic profiling (>1200 coding and non coding genes) : RNA sequencing using NextSeq 500 Illumina (60 million single-end, 150 base reads ) and analysis (using FastQC, Picard-Tools, Samtools and rseqc softwares
Measured: 2 years after blood collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2021
- Study start30 Aug 2021
- Primary completionAug 2026 (estimated)
- Study completionFeb 2027 (estimated)
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 AdrenoleukodystrophyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Fanny MOCHEL, MCU-PH, Principal investigator, Institut du Cerveau et de la Moëlle épinièreVioletta ZUJOVIC, PhD, CR1, Study chair, Institut du Cerveau et de la Moëlle épinièreCaroline SEVIN, PhD, Study director, Kremlin Bicêtre Hôpital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04925349
- Sponsor's protocol ID
- APHP190197
- Other IDs
- IDRCB
- Acronym
- MATRIX
- Status last verified
- Sep 2025
- First submitted
- 15 Apr 2019
- Last updated
- 24 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJM, Ffrench-Constant C. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013 Sep;16(9):1211-1218. doi: 10.1038/nn.3469. Epub 2013 Jul 21.
PubMed 23872599Weinhofer I, Zierfuss B, Hametner S, Wagner M, Popitsch N, Machacek C, Bartolini B, Zlabinger G, Ohradanova-Repic A, Stockinger H, Kohler W, Hoftberger R, Regelsberger G, Forss-Petter S, Lassmann H, Berger J. Impaired plasticity of macrophages in X-linked adrenoleukodystrophy. Brain. 2018 Aug 1;141(8):2329-2342. doi: 10.1093/brain/awy127.
PubMed 29860501Berger J, Forss-Petter S, Eichler FS. Pathophysiology of X-linked adrenoleukodystrophy. Biochimie. 2014 Mar;98(100):135-42. doi: 10.1016/j.biochi.2013.11.023. Epub 2013 Dec 4.
PubMed 24316281Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics. 2010 Feb;41(1):1-6. doi: 10.1055/s-0030-1253412. Epub 2010 Jun 22.
PubMed 20571983
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MATRIX - "Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia"
- ClinicalTrials.gov ID
- NCT04925349
- Acronym / sponsor ID
- MATRIX / APHP190197
- Conditions
- Adrenoleukodystrophy, Adrenomyeloneuropathy, Metachromatic Leukodystrophy, Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia
- Keywords
- Leukodystrophy, Central Nervous System Diseases, Nervous System Diseases, Immune system, Neuroinflammation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 30 Aug 2021 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 14 Jun 2021 (actual)
- 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.
This study is a national, non-randomized, open-label, multi-site with minimal risk study in adult with adrenomyeloneuropathy (AMN), childhood and adult subjects with cerebral ALD (cALD), juvenile/adult metachromatic leukodystrophy (MLD) and adults with leukoencephalopathy and axonal spheroids and pigmented glia (ALSP). 49 subjects will be enrolled with one blood sample collection during one of their medical follow-up visit.
This trial will evaluate the role of innate immunity to influence disease progression in X-ALD, MLD and ALSP, and if the mutations related to these leukodystrophies result in a specific immune response leading to the pathogenesis.
Detailed description
X-linked Adrenoleukodystrophy (X-ALD), Metachromatic Leukodystrophy (MLD) and Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) are among the most frequent inherited leukodystrophies. X-ALD and MLD can affect both children and adults, while it is thought that ALSP onset exclusively during adulthood. These three diseases are characterized by phenotypic variability and poor genotype-phenotype correlation. In childhood forms of MLD and childhood cerebral ALD (C-CALD) a devastating cerebral demyelination and neuronal degeneration lead to a rapid neurologic degradation and premature death. Patients with the adult form of X-ALD (adrenomyeloneuropathy (AMN), 60% of males) display a progressive spastic paraplegia without brain involvement. However, 20% of AMN patients will also develop cerebral ALD. Patients diagnosed with the juvenile/adult (JA-) MLD form are affected by a progressive decline of their cognitive function, followed later by that of the motor abilities. ALSP patients present a rapidly progressive neurodegenerative disorder that impairs behavioural, cognitive and motor functions.
Several arguments support the contribution of the immune response and neuroinflammation in these three leukodystrophies. In X-ALD, activation of microglia (macrophages of the CNS) plays an essential role in the acute demyelination phase, where a severe inflammatory process occurs. In ALSP, the dysfunctional protein (CSF1R) is almost exclusively expressed in microglia. Even if MLD is not considered as a neuroinflammatory disease per se, microglia activation and increased inflammatory cytokines are observed in the brain of MLD patients and mice. Even if the most commonly accepted hypothesis is that neuroinflammation is caused by secondary activation of microglia following phagocytosis of myelin debris full of undegraded material, a primitive role of the inflammation due to macrophages (MAC) dysfunction has emerged in recent years.
MATRIX proposes to explore how disease-related mutations affect key components of MAC activation responses and how it reflects on their functionality.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| affected subjects | – | Diagnostic Test: Blood sample collection* adult patients with adrenomyeloneuropathy/adrenoleukodystrophy * children with adrenoleukodystrophy * children with metachromatic leukodystrophy |
| control subjects | – | Diagnostic Test: Blood sample collection* healthy children * heatthy adults |
Who may qualify
- Ages
- 15 months to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Pediatric and adult populations. Both affected (C-CALD, AMN, A-CALD, MLD, ALSP), presymptomatic children carrying ABCD1 mutations (PRE-ALD), presymptomatic patient adults carrying CSF1R mutations (PRE-ALSP) and age-matched control subjects will be enrolled (N=10/group). Minor subjects (C-CALD, MLD, PRE-ALD and controls) will be included, based on childhood onset of C-CALD and MLD
Key inclusion criteria (13 listed)
- Boys aged between 3 and 18 years (inclusive) diagnosed with C-CALD (elevated levels of VLCFA and leukodystrophy at brain MRI)
- Boys or girls aged between 15 months and 18 years (inclusive) diagnosed with MLD (low ARSA activity and accumulation of sulfatides in urine)
- Presymptomatic boys carrying ABCD1 mutations aged between 3 and 18 years (inclusive) (PRE-ALD)
- Adult males or females aged between 18 and 60 diagnosed with MLD (low ARSA activity and accumulation of sulfatides in urine)
- Males aged between 18 and 60 years diagnosed with AMN (elevated VLCFA and clinical symptoms of AMN without leukodystrophy at brain MRI)
Key exclusion criteria (5 listed)
- Participation to a therapeutic clinical trial
- Treatment likely to modify the immune system
- Unable to have a blood collection (i.e. low hemoglobin level at the investigator's judgment)
- Any other reason, to the discretion of the investigator
- Children or adults without health insurance or social security
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 |
|---|---|---|
| Blood sample collectionblood sample collection | Diagnostic test | affected subjects, control subjects |
Primary outcome
Macrophages functionality - distribution of monocytes
Time frame: 2 years after blood collection
distribution of monocytes in the CD14-/+/++ and CD16-/+ classification using flow cytometry (% of CD14++/16-; CD14++/16+; CD14+/16+; CD14-/16-)
Macrophages functionality - myelin phagocytosis capacity
Time frame: 2 years after blood collection
percentage of myelin high, myelin low and myelin negative cells using flow cytometry
Macrophages functionality - HLA levels
Time frame: 2 years after blood collection
maximum fluorescence intensity for HLA markers using flow cytometry
2 secondary outcomes
Macrophages metabolic profiling
Time frame: 2 years after blood collection
Macrophages transcriptomic profiling
Time frame: 2 years after blood collection
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2025.
- Background: PubMed 23872599Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJM, Ffrench-Constant C. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013 Sep;16(9):1211-1218. doi: 10.1038/nn.3469. Epub 2013 Jul 21.
- Background: PubMed 29860501Weinhofer I, Zierfuss B, Hametner S, Wagner M, Popitsch N, Machacek C, Bartolini B, Zlabinger G, Ohradanova-Repic A, Stockinger H, Kohler W, Hoftberger R, Regelsberger G, Forss-Petter S, Lassmann H, Berger J. Impaired plasticity of macrophages in X-linked adrenoleukodystrophy. Brain. 2018 Aug 1;141(8):2329-2342. doi: 10.1093/brain/awy127.
- Background: PubMed 24316281Berger J, Forss-Petter S, Eichler FS. Pathophysiology of X-linked adrenoleukodystrophy. Biochimie. 2014 Mar;98(100):135-42. doi: 10.1016/j.biochi.2013.11.023. Epub 2013 Dec 4.
- Background: PubMed 20571983Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics. 2010 Feb;41(1):1-6. doi: 10.1055/s-0030-1253412. Epub 2010 Jun 22.
- Individual participant dataSharing planned: Undecided
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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.
Christelle AUGER contact
Fanny MOCHEL, MCU-PH principal investigator
Institut du Cerveau et de la Moëlle épinière
Violetta ZUJOVIC, PhD, CR1 study chair
Institut du Cerveau et de la Moëlle épinière
Caroline SEVIN, PhD study director
Kremlin Bicêtre Hôpital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adrenoleukodystrophy and Adrenomyeloneuropathy, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
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 13 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fanny MOCHEL (01 57 27 44 82, fanny.mochel@icm-institut.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Macrophages functionality - distribution of monocytes (time frame: 2 years after blood collection). The study lists 3 primary outcomes in all. 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 NCT04925349, 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 24 Sep 2025.