Diffusion Tensor Imaging (DTI) as a Tool to Identify Infants With Krabbe Disease in Urgent Need of Treatment
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Diffusion tensor imaging (DTI) of corticospinal tracts
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
Control
Children with no disease and normal enzyme levels
Motor Disability
Children at risk of developing motor disability
Krabbe Disease
Children with infantile Krabbe disease
Low Enzyme/No Krabbe Disease
Children without disease who have low enzyme levels
结局指标
主要结局
Diffusion tensor imaging (DTI) of corticospinal tracts
时间窗: at birth, 1 year and 2 years of age
次要结局
- Motor development at birth, 1 year and 2 years of age(at birth, 1 year and 2 years of age)
- Analysis of DTI-Fractional Diffusion Anisotropy (FA) values of corticospinal tracts of newborns(at age (newborn-6 weeks), 12-months and 24-months)
研究者
Deepa Soundara Rajan
Assistant Professor
University of Pittsburgh