A Natural History Study of the Gangliosidoses
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Change in Child Developmental Status as Assessed by Neuropsychological Tests
研究概览
简要总结
Hypothesis: To characterize and describe disease progression and heterogeneity of the gangliosidosis diseases.
This research study seeks to develop a quantitative method to delineate disease progression for the gangliosidosis diseases (Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis) in order to better understand the natural history and heterogeneity of these diseases. Such a quantitative method will also be essential for evaluating any treatments that may become available in the future, such as gene therapy. The data from this study will be necessary to provide end-points for future therapies, guide medical decisions about treatment, provide objective measurement of treatment outcomes, and accurately inform parents regarding potential outcomes.
详细描述
The infantile form of GM2 and GM1 gangliosidosis diseases ("classic" infantile) is the most common. Infants with Tay-Sachs disease, Sandhoff disease or GM1 gangliosidosis appear normal at birth, but at approximately 6-10 months of age begin to manifest progressive weakness and loss of muscle strength, such as loss of the ability to sit up or turn over. They may evidence deafness, and display decreased attentiveness. This is followed by rapid deterioration of motor skills and slowed mental development (neurodegeneration), often with seizures. Retinal involvement leads to visual impairment and eventual blindness. Death typically occurs by the age of five. Currently there is no treatment for Tay-Sachs disease, Sandhoff disease or GM1 gangliosidosis.
Late Onset Tay-Sachs disease ("LOTS") occurs in patients beginning in their twenties or thirties, and is characterized by poor motor coordination and psychotic behaviors. Patients with LOTS also have decreased life expectancy, although to a lesser degree than those with infantile or juvenile Tay-Sachs or Sandhoff diseases. Currently there is no treatment for LOTS.
This study is comprised of two different 'arms.' The first arm, entitled Aim 1, will focus on the developmental course of infantile and juvenile Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis. Longitudinal data from individuals with these diseases will be collected in order to delineate the natural history of these diseases. This data will help to objectify disease progression, and can be used to create a disease stage and severity index.
The second arm, entitled Aim 2, will focus on LOTS and will seek to understand the progression of central nervous system disease, with special focus upon cerebellar and frontal systems. This will be accomplished by using quantitative methods including neuroimaging and neuropsychological measures that explore motor and executive functions, visual-spatial and emotional-behavioral dysfunction.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have a documented gangliosidosis disease.
- •Subjects must be able to complete appropriate neuropsychological and neurobehavioral assessments.
- •Late-onset gangliosidosis subjects must be able to tolerate a head MRI.
排除标准
- •1. There are no exclusion criteria, beyond a desire not to participate.
研究组 & 干预措施
Gangliosidosis Diseases Study Population
This study observes one cohort: 42 infantile or juvenile Tay-Sachs disease, Sandhoff disease, or GM1 gangliosidosis affected subjects; and 10 late-onset gangliosidosis disease affected subjects.
结局指标
主要结局
Change in Child Developmental Status as Assessed by Neuropsychological Tests
时间窗: Upon enrollment; then at 12, 24, 36, 48 and 60 months
Neuropsychological testing data will be collected at baseline and annually, that measure fine and gross motor skills, visual tracking and attention, verbal and non-verbal communication, and emotional and social behaviors. For infantile and juvenile Tay-Sachs disease, Sandhoff disease and GM1 gangliosidosis-affected subjects, age- and ability-appropriate neurobehavioral and neurodevelopmental testing will include instruments such as the Bayley Scales of Infant Development (Third Edition), and the Vineland Adaptive Behavior Scales.
次要结局
- Identification of Genetic Mutation(s)(Upon Enrollment)
- Medication Regime(Upon enrollment; then at 12, 24, 36, 48 and 60 months)
- Clinical Assessments(Upon enrollment; then at 12, 24, 36, 48 and 60 months)
- Changes in Child Brain Structure Development and Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination(Upon enrollment; then at 12, 24, 36, 48 and 60 months)
- Ascertainment of Enzyme Activity Levels(Upon enrollment)
- Changes in Chitotriosidase Enzyme Activity Levels(Upon enrollment; then at 12, 24, 36, 48 and 60 months)
- Change in Adult Neurocognitive Status as Assessed by Neuropsychological Tests(Upon enrollment; then at 12, 24, 36, 48 and 60 months)
- Ascertainment of Ganglioside Levels(Upon enrollment)
- Changes in Adult Brain Structure Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination(Upon enrollment; then at 12, 24, 36, 48 and 60 months)