Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Imaging Study of the White Matter Lesions in Children With Metachromatic Leucodystrophy (HCIT-MLD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborator:
European Leukodystrophy Association
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01325025
First received: March 9, 2011
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Late Infantile Metachromatic Leukodystrophy
Other: High-field MRI (3 Teslas)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Study of the Natural History of Cerebral White Matter Involvement in Metachromatic Leukodystrophy, Using High-field MRI and Diffusion Tensor Imaging

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Assess the evolution of cortical atrophy, [ Time Frame: At inclusion (T0) and 12 months for control. At T0 then at 6 months for patients ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: November 2010
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Patients
Patients with a metachromatic leukodystrophy
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
Other Name: High-field MRI (3 Teslas)
Control
Epileptic population
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
Other Name: High-field MRI (3 Teslas)

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.

  Eligibility

Ages Eligible for Study:   1 Year to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (patients):

  • 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)

Inclusion Criteria (control):

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01325025

Contacts
Contact: Caroline Sevin, MD, PhD +33 1 45 21 31 12 caroline.sevin@inserm.fr
Contact: Laurence Lecomte, PhD ++33171196494 laurence.lecomte@nck.aphp.fr

Locations
France
Unité de recherche biomédicale, Neurospin, I2BM / DSV / SAC/ CEA, Recruiting
Gif-sur-yvette, France
Contact: Lucie Hertz-Pannier, MD, PhD    +33 1 69 08 70 98    lucie.hertz-pannier@cea.fr   
Principal Investigator: Lucie Hertz-Pannier, MD, PhD         
Bâtiment Lavoisier - Unité INSERM U 663,Hôpital Necker Enfants Malades Recruiting
Paris, France
Contact: Catherine Chiron, MD, PhD    +33 1 42 19 27 00    catherine.chiron@nck.aphp.fr   
Principal Investigator: Catherine Chiron, MD, PhD         
Service de Neurologie Pédiatrique, Hôpital Bicêtre Recruiting
Paris, France, 94275
Contact: Caroline Sevin, MD, PhD    +33 1 45 21 31 12    caroline.sevin@inserm.fr   
Principal Investigator: Caroline Sevin, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
European Leukodystrophy Association
Investigators
Principal Investigator: Caroline Sevin, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01325025     History of Changes
Other Study ID Numbers: P071232
Study First Received: March 9, 2011
Last Updated: June 13, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Metachromatic Leukodystrophy
Demyelinating Diseases
Magnetic Resonance Imaging
Diffusion Tensor Imaging
Relaxometry
Spectroscopy
Longitudinal Studies

Additional relevant MeSH terms:
Leukodystrophy, Metachromatic
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Genetic Diseases, Inborn
Hereditary Central Nervous System Demyelinating Diseases
Leukoencephalopathies
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lipidoses
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Sphingolipidoses
Sulfatidosis

ClinicalTrials.gov processed this record on November 20, 2014