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Diffusion Tensor Imaging (DTI) in Infants With Krabbe Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00787865
Recruitment Status : Active, not recruiting
First Posted : November 10, 2008
Last Update Posted : November 5, 2019
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Maria Escolar, University of Pittsburgh

Brief Summary:
This study is designed to learn about early brain development in children with Krabbe disease, and to use diffusion tensor imaging as an early diagnostic tool to identify newborns at risk for the disease.

Condition or disease
Krabbe Disease

Detailed Description:

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.

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Study Type : Observational
Estimated Enrollment : 100 participants
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
Study Start Date : April 2008
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2026

Krabbe Disease
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
Motor Disability
Children at risk of developing motor disability

Primary Outcome Measures :
  1. Diffusion tensor imaging (DTI) of corticospinal tracts [ Time Frame: at birth, 1 year and 2 years of age ]

Secondary Outcome Measures :
  1. Motor development at birth, 1 year and 2 years of age [ Time Frame: at birth, 1 year and 2 years of age ]
  2. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Children with a low levels of galactocerebrosidase, a family history of Krabbe disease or has been diagnosed with Krabbe disease, or is a child at risk of developing motor disability. Newborn screening State of New York and newborns with low enzyme.

Inclusion Criteria:

  1. Positive newborn screening test (low galactocerebrosidase)
  2. Infantile Krabbe Disease diagnosed by confirmatory low levels of residual enzyme by Dr. Wenger's Lysosmal Storage Diseases laboratory at Jefferson's Medical College (contracted by New York State) and/or carrier status established because of family history of Krabbe Disease. Patients have to be less than 6 weeks old at the time of the first assessment
  3. Children at risk of developing motor disability

Exclusion Criteria:

  1. Diagnosis or physical signs of known genetic conditions or syndromes, serious medical or neurological conditions affecting growth and development (e.g., seizure disorder, diabetes, congenital heart disease) or sensory impairments such as vision or hearing loss
  2. Children who may have suffered serious perinatal brain damage, children with birth weights less than 2000 grams and/or gestational ages of less than 34 weeks, or those with a history of intraventricular hemorrhage
  3. Children who may have a contraindication for MRI (pacemaker, vascular stents, metallic ear tubes, other metal implants or braces).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00787865

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United States, Pennsylvania
University of Pittsburgh, Children's Hospital of Pittsburgh-UPMC
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Maria Escolar
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Maria L Escolar, MD, MS University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh-UPMC
Additional Information:
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Responsible Party: Maria Escolar, Director, Program for the Study of Neurodevelopment in Rare Disorders, University of Pittsburgh Identifier: NCT00787865    
Other Study ID Numbers: PRO11050010
R01NS061965 ( U.S. NIH Grant/Contract )
First Posted: November 10, 2008    Key Record Dates
Last Update Posted: November 5, 2019
Last Verified: November 2019
Keywords provided by Maria Escolar, University of Pittsburgh:
Diffusion Tensor Imaging
Krabbe Disease
Motor Development
Motor Disability
Additional relevant MeSH terms:
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Leukodystrophy, Globoid Cell
Hereditary Central Nervous System Demyelinating Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lysosomal Storage Diseases, Nervous System
Demyelinating Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders