- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00787865
Diffusion Tensor Imaging (DTI) in Infants With Krabbe Disease
Diffusion Tensor Imaging (DTI) as a Tool to Identify Infants With Krabbe Disease in Urgent Need of Treatment
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- UPMC Children's Hospital of Pittsburgh
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Positive newborn screening test (low galactocerebrosidase)
- 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
- Children at risk of developing motor disability
Exclusion Criteria:
- 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
- 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
- Children who may have a contraindication for MRI (pacemaker, vascular stents, metallic ear tubes, other metal implants or braces).
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Krabbe Disease
Children with infantile Krabbe disease
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Low Enzyme/No Krabbe Disease
Children without disease who have low enzyme levels
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Control
Children with no disease and normal enzyme levels
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Motor Disability
Children at risk of developing motor disability
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Diffusion tensor imaging (DTI) of corticospinal tracts
Time Frame: at birth, 1 year and 2 years of age
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at birth, 1 year and 2 years of age
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Motor development at birth, 1 year and 2 years of age
Time Frame: at birth, 1 year and 2 years of age
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at birth, 1 year and 2 years of age
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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
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at age (newborn-6 weeks), 12-months and 24-months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Deepa S Rajan, MD, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh-UPMC
Publications and helpful links
General Publications
- Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81. doi: 10.1056/NEJMoa042604.
- Provenzale JM, Escolar M, Kurtzberg J. Quantitative analysis of diffusion tensor imaging data in serial assessment of Krabbe disease. Ann N Y Acad Sci. 2005 Dec;1064:220-9. doi: 10.1196/annals.1340.040.
Study record dates
Study Major Dates
Study Start
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Demyelinating Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Leukoencephalopathies
- Hereditary Central Nervous System Demyelinating Diseases
- Leukodystrophy, Globoid Cell
Other Study ID Numbers
- STUDY20020124
- R01NS061965 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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