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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Study of the Natural History of Cerebral White Matter Involvement in Metachromatic Leukodystrophy, Using High-field MRI and Diffusion Tensor Imaging

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 Summary:

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
Sponsor: Assistance Publique - Hôpitaux de Paris

Current 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.


Original Primary Outcome: Assess the natural history of the white matter and cortex lesions in MLD using diffusion tensor imaging (DTI)/ high field MRI. [ Time Frame: At inclusion for control (T0) and patients then at 4, 8,12 and 18 months only 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.


Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • Assess the natural history of the white matter and cortex lesions in MLD using using multi-voxel spectroscopic imaging. [ Time Frame: At inclusion for control (T0) and patients then at 4, 8,12 and 18 months only for patients ]
  • Assess the evolution of cortical atrophy, [ Time Frame: At inclusion for control (T0) and patients then at 4, 8,12 and 18 months only for patients ]
  • Correlate the neuroimaging parameters with motor function measure (Gross Motor Function Measure) and cognitive tests (BSID, WPPSI). [ Time Frame: At inclusion for control (T0) and patients then at 4, 8,12 and 18 months only for patients ]


Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: March 9, 2011
Date Started: November 2010
Date Completion:
Last Updated: July 31, 2016
Last Verified: July 2016