Diffusion Tensor Imaging (DTI) in Infants With Krabbe Disease
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Diffusion Tensor Imaging (DTI) as a Tool to Identify Infants With Krabbe Disease in Urgent Need of Treatment|
- Diffusion tensor imaging (DTI) of corticospinal tracts [ Time Frame: at birth, 1 year and 2 years of age ] [ Designated as safety issue: No ]
- Motor development at birth, 1 year and 2 years of age [ Time Frame: at birth, 1 year and 2 years of age ] [ Designated as safety issue: No ]
- Analysis of DTI-Fractional Diffusion Anisotropy (FA) values of corticospinal tracts of newborns [ Time Frame: at age (newborn-6 weeks), 12-months and 24-months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2008|
|Estimated Study Completion Date:||April 2025|
|Estimated Primary Completion Date:||April 2020 (Final data collection date for primary outcome measure)|
Children with infantile Krabbe disease
Low Enzyme/No Krabbe Disease
Children without disease who have low enzyme levels
Children with no disease and normal enzyme levels
Children at risk of developing motor disability
This study is designed to learn about early brain development in children with Krabbe disease and to use diffusion tensor imaging (DTI) as an early diagnostic tool to differentiate children with infantile Krabbe disease from newborns who are disease free but have very low enzyme levels. Additionally, this study will determine how certain structures in the brain will develop over 24 months in children with infantile Krabbe disease and those without disease who have low enzyme levels. This study will also reveal information about the learning and motor development of children, and will help researchers predict outcomes after treatment.
Krabbe disease is a rare, childhood neurodegenerative disorder caused by galactocerebrosidase deficiency. It results in rapid demyelination, progressive spasticity, mental deterioration, blindness, deafness, seizures, and death. Based on previously published findings, treatment with unrelated umbilical cord blood transplantation is now standard for Krabbe disease, provided that the treatment occurs within the first weeks of life and before symptoms appear.
Once newborns are identified through population screening, there is no objective measure to predict if the baby will develop the most frequent rapidly progressive infantile forms of Krabbe or have a slower juvenile or adult form. Phenotype and genotype correlations are not possible because there are more than 150 mutations that can cause the disease and many polymorphisms in the normal population that affect the enzyme level.
There is an urgent clinical need to develop a predictive measure. To date, there are no available tools to classify infants into the infantile versus later forms. New advances in neuroimaging techniques have enabled scientists to quantify changes in brain growth and myelination early in life and before disease symptoms develop.
Knowledge from this study will help identify the window of opportunity for early intervention and treatment to prevent severe disability, and may lead to better treatment strategies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00787865
|United States, Pennsylvania|
|University of Pittsburgh, Children's Hospital of Pittsburgh-UPMC|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Maria L Escolar, MD, MS||University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh-UPMC|