Imaging Study of the White Matter Lesions in Children With Metachromatic Leucodystrophy

NCT ID: NCT01325025

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2016-07-31

Brief 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 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.

Conditions

Late Infantile Metachromatic Leukodystrophy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Patients

Patients with a metachromatic leukodystrophy

Group Type: OTHER

High-field MRI (3 Teslas)

Intervention Type: 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

Control

Epileptic population

Group Type: OTHER

High-field MRI (3 Teslas)

Intervention Type: 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

Interventions

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

Intervention Type: OTHER

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• Evolutive heart, pulmonary, renal or gastrointestinal disease
• Contra-indication to sedation
• Contra-indication to MRI (implanted magnetic material)

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Leukodystrophy Association

OTHER

Sponsor Role: collaborator

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Caroline Sevin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Unité de recherche biomédicale, Neurospin, I2BM / DSV / SAC/ CEA,

Gif-sur-Yvette, , France

Service de Neurologie Pédiatrique, Hôpital Bicêtre

Paris, , France

Bâtiment Lavoisier - Unité INSERM U 663,Hôpital Necker Enfants Malades

Paris, , France

Countries

France

Other Identifiers

P071232

Identifier Type: -

Identifier Source: org_study_id