Late Infantile Metachromatic LeukodystrophyHCIT-MLDNCT01325025
Imaging Study of the White Matter Lesions in Children With Metachromatic Leucodystrophy
A study testing High-field MRI (3 Teslas) in people with Late Infantile Metachromatic Leukodystrophy, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
Trial summary
High-field MRI and diffusion tensor imaging with 3D reconstruction of the myelin tracks, in combination with multivoxel proton spectroscopy, will allow to precise more accurately the evolution of the white matter lesions in patients affected with Metachromatic Leukodystrophy (particularly in the initial phase of the… Read more about this study
- Who is it for?
- Ages 1 year to 6 years
- Conditions the study is for
- Late Infantile Metachromatic Leukodystrophy
- What is being tested?
- High-field MRI (3 Teslas)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 3 sitesFrance
- Study dates
- Nov 2010to Jul 2016
- Phase
- Interventional
- 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 1 year to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children with proven metachromatic leukodystrophy (MLD) with decreased activity of arylsulfatase A enzyme in leukocytes and abnormal excretion of urinary sulfatides
- Age ≥ 1 year and ≤ 6 years
- Recently diagnosed (within < 18 months)
- Children with partial cryptogenic epilepsy or with a suspected brain lesion on conventional MRI, who should have high-field MRI to detect structural abnormalities that could benefit from surgical resection
- Age ≥ 1 year and ≤ 6 years
Who cannot join
- Evolutive heart, pulmonary, renal or gastrointestinal disease
- Contra-indication to sedation
- Contra-indication to MRI (implanted magnetic material)
Trial locations and contacts
3 sites in 1 country.
France3 sites
Unité de recherche biomédicale, Neurospin, I2BM / DSV / SAC/ CEA,
Gif-sur-Yvette
Service de Neurologie Pédiatrique, Hôpital Bicêtre
Paris, 94275
Bâtiment Lavoisier - Unité INSERM U 663,Hôpital Necker Enfants Malades
Paris
About this study
Official title: Study of the Natural History of Cerebral White Matter Involvement in Metachromatic Leukodystrophy, Using High-field MRI and Diffusion Tensor Imaging
High-field MRI and diffusion tensor imaging with 3D reconstruction of the myelin tracks, in combination with multivoxel proton spectroscopy, will allow to precise more accurately the evolution of the white matter lesions in patients affected with Metachromatic Leukodystrophy (particularly in the initial phase of the disease). This will increase the knowledge of the disease and provide new indicators for the selection and evaluation of patients eligible for new therapeutic approaches.
Read the detailed description
Metachromatic Leukodystrophy (MLD) is a rare autosomal recessive disorder caused by the deficiency of the Arylsulfatase A enzyme (ARSA), resulting in accumulation of galactosyl sulfatide (cerebroside sulfate), a major constituent of the myelin sheath. Accumulation of sulfatides leads to a progressive degeneration of the white matter in the central and peripheral nervous systems (CNS, PNS) and to a neuronal degeneration. The late-infantile form of MLD, which is usually diagnosed in the second year of life, is the most frequent and severe form of the disease. The prognosis is severe, leading to vegetative stage or death within few years after the diagnosis. There is no treatment for patients affected with this early-onset form of the disease.
Conventional MRI (1.5 Tesla) shows extensive involvement of the cerebral white matter (hypo-T1, hyper- T2 and FLAIR signals) indicative of rapidly progressing leukodystrophy. Early cortical atrophy reflects associated neuronal involvement. Proton MR spectroscopy demonstrates abnormalities of choline and N-acetyl-aspartate (demyelination, neuronal loss), which are non-specific but can serve as indicators to monitor the effects of any therapeutic intervention.
In early-onset forms of MLD, conventional MRI becomes abnormal at a relatively advanced stage of the disease and the neuroradiological diagnosis may be difficult before the age of 2 - 2 1/2 years of age. Moreover, topography and extent of detectable lesions are poorly correlated with the disease severity.
In order to improve information provided by neuroimaging, this study aims to investigate prospectively and longitudinally (over a period of 6 months) white and grey matter lesions in 10 MLD children aged 1 to 6 years, using high-field MRI (3 Teslas) and diffusion tensor imaging (DTI) with 3D reconstruction of the myelin tracks. The time interval between diagnosis and inclusion will not exceed 18 months, thus patients will be included at an early stage of their disease. Each time-point (T0 and 6 months) will also include neurological evaluation to correlate the imaging, cognitive and motor functions. Children will be included over a period of 5 years. The total duration of the study will be 5.5 years. Controls will include 25 age-matched children with cryptogenic partial epilepsy who should have a high-field MRI to detect structural abnormalities. Controls will have a MRI and cognitive evaluation at T0 and 12 months if necessary. This study will increase our knowledge of the natural history of MLD and provide new indicators for the selection and evaluation of patients eligible for new therapeutic approaches.
- Being tested
- High-field MRI (3 Teslas)
- Keywords
- Metachromatic Leukodystrophy, Demyelinating Diseases, Magnetic Resonance Imaging, Diffusion Tensor Imaging, Relaxometry, Spectroscopy, Longitudinal Studies
- Medical subject headings
- Leukodystrophy, Metachromatic, Demyelinating Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-field MRI (3 Teslas)Other
- anatomical location
- conventional anatomical sequence T1, T2, FLAIR
- diffusion tensor sequence (21 directions)
- high angular resolution diffusion (HARDI) sequence
- field map
- reflexology T1, T2
- spectroscopic imaging sequence
High-field MRI (3 Teslas)Other
- anatomical location
- conventional anatomical sequence T1, T2, FLAIR
- diffusion tensor sequence (21 directions)
- high angular resolution diffusion (HARDI) sequence
- field map
- reflexology T1, T2
- spectroscopic imaging sequence
| Study group | Role | What they receive |
|---|---|---|
| Patients | Other | Patients with a metachromatic leukodystrophy Receives: Other: High-field MRI (3 Teslas) |
| Control | Other | Epileptic population Receives: Other: High-field MRI (3 Teslas) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the natural history of the white matter and cortex lesions in MLD using diffusion tensor imaging (DTI)and relaxometry/ high field MRI.
The following parameters will be studied: quantitative measurements of mean diffusivity, longitudinal and transverse fractional anisotropy in ROIs (regions of interest), 3D-tractographic reconstruction of the myelin tracks.
Measured: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients
Secondary outcomes (3)
Assess the natural history of the white matter and cortex lesions in MLD using using multi-voxel spectroscopic imaging.
Measured: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients
Assess the evolution of cortical atrophy,
Measured: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients
Correlate the neuroimaging parameters with motor function measure (Gross Motor Function Measure) and cognitive tests (BSID, WPPSI).
Measured: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2011 (estimated)
- Study startNov 2010
- Primary completionMar 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Late Infantile Metachromatic LeukodystrophyStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- European Leukodystrophy Association, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Caroline Sevin, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01325025
- Sponsor's protocol ID
- P071232
- Acronym
- HCIT-MLD
- Status last verified
- Sep 2025
- First submitted
- 9 Mar 2011
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Natural History of Cerebral White Matter Involvement in Metachromatic Leukodystrophy, Using High-field MRI and Diffusion Tensor Imaging
- ClinicalTrials.gov ID
- NCT01325025
- Acronym / sponsor ID
- HCIT-MLD / P071232
- Keywords
- Metachromatic Leukodystrophy, Demyelinating Diseases, Magnetic Resonance Imaging, Diffusion Tensor Imaging, Relaxometry, Spectroscopy, Longitudinal Studies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- European Leukodystrophy Association, URC-CIC Paris Descartes Necker Cochin
- Study start
- Nov 2010
- Primary completion
- Mar 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 29 Mar 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.
High-field MRI and diffusion tensor imaging with 3D reconstruction of the myelin tracks, in combination with multivoxel proton spectroscopy, will allow to precise more accurately the evolution of the white matter lesions in patients affected with Metachromatic Leukodystrophy (particularly in the initial phase of the disease). This will increase the knowledge of the disease and provide new indicators for the selection and evaluation of patients eligible for new therapeutic approaches.
Detailed description
Metachromatic Leukodystrophy (MLD) is a rare autosomal recessive disorder caused by the deficiency of the Arylsulfatase A enzyme (ARSA), resulting in accumulation of galactosyl sulfatide (cerebroside sulfate), a major constituent of the myelin sheath. Accumulation of sulfatides leads to a progressive degeneration of the white matter in the central and peripheral nervous systems (CNS, PNS) and to a neuronal degeneration. The late-infantile form of MLD, which is usually diagnosed in the second year of life, is the most frequent and severe form of the disease. The prognosis is severe, leading to vegetative stage or death within few years after the diagnosis. There is no treatment for patients affected with this early-onset form of the disease.
Conventional MRI (1.5 Tesla) shows extensive involvement of the cerebral white matter (hypo-T1, hyper- T2 and FLAIR signals) indicative of rapidly progressing leukodystrophy. Early cortical atrophy reflects associated neuronal involvement. Proton MR spectroscopy demonstrates abnormalities of choline and N-acetyl-aspartate (demyelination, neuronal loss), which are non-specific but can serve as indicators to monitor the effects of any therapeutic intervention.
In early-onset forms of MLD, conventional MRI becomes abnormal at a relatively advanced stage of the disease and the neuroradiological diagnosis may be difficult before the age of 2 - 2 1/2 years of age. Moreover, topography and extent of detectable lesions are poorly correlated with the disease severity.
In order to improve information provided by neuroimaging, this study aims to investigate prospectively and longitudinally (over a period of 6 months) white and grey matter lesions in 10 MLD children aged 1 to 6 years, using high-field MRI (3 Teslas) and diffusion tensor imaging (DTI) with 3D reconstruction of the myelin tracks. The time interval between diagnosis and inclusion will not exceed 18 months, thus patients will be included at an early stage of their disease. Each time-point (T0 and 6 months) will also include neurological evaluation to correlate the imaging, cognitive and motor functions. Children will be included over a period of 5 years. The total duration of the study will be 5.5 years. Controls will include 25 age-matched children with cryptogenic partial epilepsy who should have a high-field MRI to detect structural abnormalities. Controls will have a MRI and cognitive evaluation at T0 and 12 months if necessary. This study will increase our knowledge of the natural history of MLD and provide new indicators for the selection and evaluation of patients eligible for new therapeutic approaches.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | Other | Other: High-field MRI (3 Teslas)Patients with a metachromatic leukodystrophy |
| Control | Other | Other: High-field MRI (3 Teslas)Epileptic population |
Who may qualify
- Ages
- 1 year to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Children with proven metachromatic leukodystrophy (MLD) with decreased activity of arylsulfatase A enzyme in leukocytes and abnormal excretion of urinary sulfatides
- Age ≥ 1 year and ≤ 6 years
- Recently diagnosed (within < 18 months)
- Children with partial cryptogenic epilepsy or with a suspected brain lesion on conventional MRI, who should have high-field MRI to detect structural abnormalities that could benefit from surgical resection
- Age ≥ 1 year and ≤ 6 years
Key exclusion criteria (3 listed)
- Evolutive heart, pulmonary, renal or gastrointestinal disease
- Contra-indication to sedation
- Contra-indication to MRI (implanted magnetic material)
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 |
|---|---|---|
| High-field MRI (3 Teslas)* anatomical location * conventional anatomical sequence T1, T2, FLAIR * diffusion tensor sequence (21 directions) * high angular resolution diffusion (HARDI) sequence * field map * reflexology T1, T2 * spectroscopic imaging sequence | Other | Patients |
| High-field MRI (3 Teslas)* anatomical location * conventional anatomical sequence T1, T2, FLAIR * diffusion tensor sequence (21 directions) * high angular resolution diffusion (HARDI) sequence * field map * reflexology T1, T2 * spectroscopic imaging sequence | Other | Control |
Primary outcome
Assess the natural history of the white matter and cortex lesions in MLD using diffusion tensor imaging (DTI)and relaxometry/ high field MRI.
Time frame: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients
The following parameters will be studied: quantitative measurements of mean diffusivity, longitudinal and transverse fractional anisotropy in ROIs (regions of interest), 3D-tractographic reconstruction of the myelin tracks.
3 secondary outcomes
Assess the natural history of the white matter and cortex lesions in MLD using using multi-voxel spectroscopic imaging.
Time frame: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients
Assess the evolution of cortical atrophy,
Time frame: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients
Correlate the neuroimaging parameters with motor function measure (Gross Motor Function Measure) and cognitive tests (BSID, WPPSI).
Time frame: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients
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 20 Nov 2025.
- Individual participant dataSharing planned: No
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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.
Caroline Sevin, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-field MRI (3 Teslas) in people with Late Infantile Metachromatic Leukodystrophy, run by Assistance Publique - Hôpitaux de Paris at 3 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 5 inclusion and 3 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 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
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?
Assess the natural history of the white matter and cortex lesions in MLD using diffusion tensor imaging (DTI)and relaxometry/ high field MRI. (time frame: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Nov 2025.