Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06512649
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-06-03
Brief Title:
Early Recognition and Intervention in Siblings at High-risk for Neurodevelopmental Disorder
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Early Recognition and Intervention in Siblings at High-risk for Neurodevelopmental Disorder
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ERI-SIBS
Brief Summary:
H1The primary goal of this intervention study is to learn if very early parent-mediated intervention in children at risk for neurodevelopmental disorders in the first year of life can be implemented in routine care positively impacting early sensory-motor and socio-communicative developmental trajectories and reducing the developmental gap in children with signs of concern
H2 It is here postulated that early intervention with active parental involvement can reduce parental stress as well as improve parental understanding and responsiveness to the childs communication cues
H3 An important part of our work will be analysing data about early social and joint attention behaviours in recruited children and comparing them at different time points The hypothesis is to find early differences between groups at baseline and to detect a change before and after the intervention For this reason in our study design we decided to use technologies to collect data on quantitative measures during play-structured and laboratory sessions to understand changes in developmental trajectories
H4 Given the potential role of genetic and immunological mechanisms in ASD one of the studys secondary aims is to investigate the impact of an early intervention programme on epigenetic changes and inflammatory and immune response
After enrolment and baseline assessments T0 children will be allocated to the three groups
Group 1 - Clinical Monitoring Group CM Siblings of TD children subjects with no signs of concern
Group 2 - Active Monitoring Group AM Siblings of ASD children with no signs of concern
Group 3 - Early Intervention Group EI Siblings classified as with signs of concern at baseline evaluation
All children will be re-evaluated after 6 months T1 and after 12 months T2
H2 It is here postulated that early intervention with active parental involvement can reduce parental stress as well as improve parental understanding and responsiveness to the childs communication cues
H3 An important part of our work will be analysing data about early social and joint attention behaviours in recruited children and comparing them at different time points The hypothesis is to find early differences between groups at baseline and to detect a change before and after the intervention For this reason in our study design we decided to use technologies to collect data on quantitative measures during play-structured and laboratory sessions to understand changes in developmental trajectories
H4 Given the potential role of genetic and immunological mechanisms in ASD one of the studys secondary aims is to investigate the impact of an early intervention programme on epigenetic changes and inflammatory and immune response
After enrolment and baseline assessments T0 children will be allocated to the three groups
Group 1 - Clinical Monitoring Group CM Siblings of TD children subjects with no signs of concern
Group 2 - Active Monitoring Group AM Siblings of ASD children with no signs of concern
Group 3 - Early Intervention Group EI Siblings classified as with signs of concern at baseline evaluation
All children will be re-evaluated after 6 months T1 and after 12 months T2
Detailed Description:
Researchers will contact interested parents to assess eligibility and provide detailed study information Parents will provide written consent before completing baseline assessments T0 and based on the scores at the main outcome measures children will be assigned to the correct group Infants with no signs of concern and siblings of TD children will be allocated to Group 1 CM infants with no signs of concern scores at the Griffiths-3 and CSBS-ITC in the normal range and siblings of ASD children will be allocated to Group 2 AM infants with General Quotient score below 85 using Griffiths-3 andor at least one score above the concern cutoff using the CSBS-ITC will be allocated to Group 3 EI Families allocated to Groups 2 and 3 will start the intervention within one month from the baseline assessment Families allocated to Group 1 will perform only the evaluations at different time points Assessments will be conducted at baseline T0 which will be when the parents give their consent and within the 8 months of life of the child after 6 months from the start of the intervention T1 and after 12 months from the start of the intervention T2
Technological assessment of social behaviour and joint attention
- video recording of ESCP through Kinect Azure camera to collect and analyse quantitative data related to joint attention
The administration of the ECSP-I will be video-recorded through an Azure Kinect camera to extract automatically gaze orientation and quantitatively assess Joint Attention
- Eye-tracker acquisitions An experimental Eye-Tracker Screening ETS protocol for children will also be developed Specifically short videos will be used to measure the childrens ability to process familiarunfamiliar faces and to respond to social stimuli particularly referential gaze The childrens eye movements will be analysed using the eye-tracker Tobii Pro Fusion and extracted using the appropriate software
At recruitment T0 anamnestic sociodemographic data and auxological and clinical parameters at birth will be collected
Biomolecular assessment Saliva samples will be collected using 3 different kits respectively for DNA or RNA extraction and for protein detection through spongy swabs that are inserted into the babys mouth leading the saliva collection non-invasive simple fast and most importantly painless Saliva samples will be collected from all the probands at T0 T1 and T2 and from their siblings and parents at T0 to assess parent-to-child genetic transmission in relation to the risk of ASD If possible a sample of approximately 40 mL of blood from the parents will be collected
Biological samples from family quartet will be collected as follow
1 In all the enrolled children their older siblings and parents genetic analysis will be conducted by a Next-Generation Sequencing NGS gene-targeted panel approach to analyse genes involved in synaptogenesis and immunogenetic regulation
2 Epigenetic analysis of the miRNome in saliva collected from all enrolled children at all time-points will be performed by NGS Epigenetic analysis will allow to define a panel of microRNAs that can differentiate between ASD children and children with typical development
3 Analysis of inflammatory cytokines and neurotrophic factors using an automated immunoassay system ELLA Biotech will be performed in probands at T0 T1 and T2 Parents will also be characterized for cytokine and lymphocyte subset at T0
Correlations between clinical parameters and all biological variables genetic epigenetic inflammatory will be performed to correlate molecular biomarkers with neurodevelopmental changes in follow-up and pre-post intervention
Sample size
Since the importance of ECSP-I in this project as behavioural outcome measures as a tool for reaching quantitative data through technology we calculate the sample size to detect an association between the ECSP-I score and the groups 1 2 and 3 at each time point The calculation was performed based on preliminary data not already published from the Italian Version of ESCP ECSP-I Assuming a standard deviation of 056 for the ECSP-I scale and a significance level α 0 01 obtained by applying the Bonferroni correction for multiple comparisons performed in pairs between groups to the type I error we obtained a sample size of 14 subjects per group to detect a difference of 08 between the means of each group using a 2-tailed Students t-test for independent samples with a power of 80 Assuming a drop-out rate of 10 the required sample size increases to 16 subjects per group that is 48 subjects in total
Statistical analysis
Analysis using STATA or SPSS 2800 will follow standard methods for trials using comparisons between the three groups First a study of the maturation trajectories of the infants will be carried out with a description of the pre-post intervention changes in the tests carried out Secondly quantitative evaluations of joint attention data and molecular markers will be performed detected and described through mean and standard deviation in case of Gaussian distribution of variables or median and interquartile range in case of non-Gaussian distribution The normality of distributions will be assessed by applying the Shapiro-Wilk test For categorical variables absolute frequencies and percentages will be reported Genetic analysis of intra-familial allelic inheritance will be conducted by AFBAC Affected Family-Based Controls and TDT Transmission Disequilibrium Test The immunological parameters obtained from the groups of ASD children and children with typical development will be analysed using a nonparametric Mann-Whitney test that will allow to identification of specific immunological biomarkers of ASD-associated neuroinflammation Moreover clinical parameters will be correlated with immunological biomarkers characteristic of ASD children Finally epigenetic analysis will allow us to define a panel of microRNAs that can differentiate between ASD children and children with typical development Using computer algorithms the potential targets pathways and biological functions deregulated by this group of miRNAs will be analysed These data will also be analysed concerning the clinical parameters evaluated in the study and both the genetic and inflammatory characterization of the subjects studied
Technological assessment of social behaviour and joint attention
- video recording of ESCP through Kinect Azure camera to collect and analyse quantitative data related to joint attention
The administration of the ECSP-I will be video-recorded through an Azure Kinect camera to extract automatically gaze orientation and quantitatively assess Joint Attention
- Eye-tracker acquisitions An experimental Eye-Tracker Screening ETS protocol for children will also be developed Specifically short videos will be used to measure the childrens ability to process familiarunfamiliar faces and to respond to social stimuli particularly referential gaze The childrens eye movements will be analysed using the eye-tracker Tobii Pro Fusion and extracted using the appropriate software
At recruitment T0 anamnestic sociodemographic data and auxological and clinical parameters at birth will be collected
Biomolecular assessment Saliva samples will be collected using 3 different kits respectively for DNA or RNA extraction and for protein detection through spongy swabs that are inserted into the babys mouth leading the saliva collection non-invasive simple fast and most importantly painless Saliva samples will be collected from all the probands at T0 T1 and T2 and from their siblings and parents at T0 to assess parent-to-child genetic transmission in relation to the risk of ASD If possible a sample of approximately 40 mL of blood from the parents will be collected
Biological samples from family quartet will be collected as follow
1 In all the enrolled children their older siblings and parents genetic analysis will be conducted by a Next-Generation Sequencing NGS gene-targeted panel approach to analyse genes involved in synaptogenesis and immunogenetic regulation
2 Epigenetic analysis of the miRNome in saliva collected from all enrolled children at all time-points will be performed by NGS Epigenetic analysis will allow to define a panel of microRNAs that can differentiate between ASD children and children with typical development
3 Analysis of inflammatory cytokines and neurotrophic factors using an automated immunoassay system ELLA Biotech will be performed in probands at T0 T1 and T2 Parents will also be characterized for cytokine and lymphocyte subset at T0
Correlations between clinical parameters and all biological variables genetic epigenetic inflammatory will be performed to correlate molecular biomarkers with neurodevelopmental changes in follow-up and pre-post intervention
Sample size
Since the importance of ECSP-I in this project as behavioural outcome measures as a tool for reaching quantitative data through technology we calculate the sample size to detect an association between the ECSP-I score and the groups 1 2 and 3 at each time point The calculation was performed based on preliminary data not already published from the Italian Version of ESCP ECSP-I Assuming a standard deviation of 056 for the ECSP-I scale and a significance level α 0 01 obtained by applying the Bonferroni correction for multiple comparisons performed in pairs between groups to the type I error we obtained a sample size of 14 subjects per group to detect a difference of 08 between the means of each group using a 2-tailed Students t-test for independent samples with a power of 80 Assuming a drop-out rate of 10 the required sample size increases to 16 subjects per group that is 48 subjects in total
Statistical analysis
Analysis using STATA or SPSS 2800 will follow standard methods for trials using comparisons between the three groups First a study of the maturation trajectories of the infants will be carried out with a description of the pre-post intervention changes in the tests carried out Secondly quantitative evaluations of joint attention data and molecular markers will be performed detected and described through mean and standard deviation in case of Gaussian distribution of variables or median and interquartile range in case of non-Gaussian distribution The normality of distributions will be assessed by applying the Shapiro-Wilk test For categorical variables absolute frequencies and percentages will be reported Genetic analysis of intra-familial allelic inheritance will be conducted by AFBAC Affected Family-Based Controls and TDT Transmission Disequilibrium Test The immunological parameters obtained from the groups of ASD children and children with typical development will be analysed using a nonparametric Mann-Whitney test that will allow to identification of specific immunological biomarkers of ASD-associated neuroinflammation Moreover clinical parameters will be correlated with immunological biomarkers characteristic of ASD children Finally epigenetic analysis will allow us to define a panel of microRNAs that can differentiate between ASD children and children with typical development Using computer algorithms the potential targets pathways and biological functions deregulated by this group of miRNAs will be analysed These data will also be analysed concerning the clinical parameters evaluated in the study and both the genetic and inflammatory characterization of the subjects studied
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None