Late Infantile Metachromatic Leukodystrophy Clinical Trial
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.
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.
;
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00633139 -
Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
|
Phase 1/Phase 2 | |
| Terminated |
NCT00681811 -
Open-Label Extension Study of Recombinant Human Arylsulfatase A (HGT-1111) in Late Infantile MLD
|
Phase 2 |