Diffusion Tensor Imaging (DTI) in Infants With Krabbe Disease

This study is ongoing, but not recruiting participants.
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Maria Escolar, University of Pittsburgh
ClinicalTrials.gov Identifier:
First received: November 7, 2008
Last updated: February 11, 2016
Last verified: February 2016
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.

Krabbe Disease

Study Type: Observational
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

Resource links provided by NLM:

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Diffusion tensor imaging (DTI) of corticospinal tracts [ Time Frame: at birth, 1 year and 2 years of age ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 100
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)
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

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.


Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
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).
  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: NCT00787865

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)
Principal Investigator: Maria L Escolar, MD, MS University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh-UPMC
  More Information

Responsible Party: Maria Escolar, Director, Program for the Study of Neurodevelopment in Rare Disorders, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00787865     History of Changes
Other Study ID Numbers: PRO11050010  R01NS061965 
Study First Received: November 7, 2008
Last Updated: February 11, 2016
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Diffusion Tensor Imaging
Krabbe Disease
Motor Development
Motor Disability

Additional relevant MeSH terms:
Leukodystrophy, Globoid Cell
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Genetic Diseases, Inborn
Hereditary Central Nervous System Demyelinating Diseases
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases

ClinicalTrials.gov processed this record on May 25, 2016