Omic Profile in Autism Spectrum Disorder: From Cellular Level Towards Future Treatments
概览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Measurement of severity of ASD core symptoms with ADOS2
概览
简要总结
This is an interventional non pharmacological study in pediatric patientis affected by Autism Spectrum Disorder. It ams to create a collection of iPSCs and hiNSCs derived from deeply characterized ASD patients, to omics-characterize the cells, and to study the behavioral pattern of microglia-like cells in the onset of ASD.
详细描述
ASD is a neurodevelopmental disorder affecting about 1 in 36 children and with a frequency increasing over time, thus delineating a significant social and public health problem that needs to be faced, as well as an important field of study and research.
This project starts from the idea that complex diseases such as ASD must be tackled with a multidisciplinary approach.
The investigators are collecting a large number of somatic cells from ASD patients who have been highly characterized and stratified in subgroups from a clinical, genetic, neurological and neuropsychological point and reprogramming these cells into induced pluripotent stem cells from which the cells of three embryonic germ layers originate.
Combining the expertise of the two Units, the project will have two short-term results:
- a large collection of cell models from highly characterized ASD patients that can be shared with scientific community to speed up the understanding of the causes of the disease
- the knowledge of pathological pathways of cells belonging to well characterized patients: omic analyses will be correlated to clinical/genetic data to understand if a specific subgroup has specific omic profile or the same profile is common to all ASD subgroups, if a specific clinical feature or genetic polymorphism is correlated with omic data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Defined ASD diagnosis according to DSM-5 criteria
- •Age 3-15 years
- •Informed consent signed by the guardians/legal representatives.
排除标准
- •Exclusion criteria for Group 1 will be: having a defined genetic diagnosis or an overall clinical presentation strongly suggestive for a syndromic condition. For this definition we will apply the criteria ASD associated with at least one of the following: \>=3 facial anomalies, \>=1 major/\>=2 minor malformation (following EUROCAT classification), clinical issue affecting \>=2 systems. Children showing such phenotypes but having no current genetic diagnosis could not be included in the study. Patients with a syndromic presentation and confirmed genetic diagnosis will be included in the Syndromic Group
- •No standardized test to establish diagnosis
- •Parents refusing to complete the consent form
- •Impossible blood sample collection.
研究组 & 干预措施
Single arm study
the arm is constituted by 100 pediatric patients (aged -15) with ASD diagnosis
干预措施: Blood sample collection for ASD cells model production and Omic studies (Biological)
结局指标
主要结局
Measurement of severity of ASD core symptoms with ADOS2
时间窗: 1 year
Outcome unity of measure: Calibrated Severity Scores - Measure range: 1-10
Measurement of severity of ASD core symptoms with SRS 2
时间窗: 1 year
Outcome unity of measure: T-score - Measure range: 30-90
Measurement of developmental abilities with Griffiths III scales
时间窗: 1 year
Outcome unity of measure: GQ - Measure range: \<20-150
Measurement of cognitive abilities with Wechsler scales
时间窗: 1 year
Outcome unity of measure: IQ - Measure range: \<20-160
Measurement of cognitive abilities with Leiter 3 scales
时间窗: 1 year
Outcome unity of measure: IQ - Measure range: 40-160
Quantification of emotional and behavioral problems with CBCL
时间窗: 1 year
Outcome unity of measure: Raw score - Measure range: 0-200 for children \<6 years old / and 0-226 for children 6-18 years old
Verification on iPSs of presence/absence of expression of stem cell genes and genes from the three embryonic layers
时间窗: 1 year
Outcome unity of measure: Gene expression - Measure range: yes/no
Percentage of hiNSCs differentiating into astrocytes, oligodendrocytes, and neurons
时间窗: 1 year
Outcome unity of measure: % cells differentiated/tot numeber of cells - Measure range: 0-100%
Measurement of length of neurite growth in hiNSCs
时间窗: 1 year
Outcome unity of measure: µm - Measure range 0-500 µm
Measurement of concentration of distinct lipid molecular species in ASD derived cells and control derived cells in order to assess the differences in lipidomic profiles
时间窗: 1 year
Outcome unity of measure: µmol/L - Measure range: 0.001 µmol/L - \>10,000 µmol/L
次要结局
未报告次要终点