Ignite Creation Date:
2024-05-06 @ 4:15 PM
Last Modification Date:
2024-10-26 @ 2:06 PM
Study NCT ID:
NCT04923854
Status:
RECRUITING
Last Update Posted:
2022-04-18
First Post:
2021-06-07
Brief Title:
Phenotypic Exploration of Autism Spectrum Disorders Retrospective and Prospective Data
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Phenotypic Exploration of Autism Spectrum Disorders Retrospective and Prospective Data
Status:
RECRUITING
Status Verified Date:
2021-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EXPECT
Brief Summary:
Autism Spectrum Disorders ASD are a heterogeneous group of severe developmental abnormalities of the nervous system characterized by deficits in social interaction and verbal and nonverbal communication affecting approximately 1 of the general population
In 5-40 of cases genetic factors are identified as the cause of these disorders
Despite this unique definition and the advancement of techniques ASD is still a clinically and genetically heterogeneous condition as several hundred genes have been identified to date
Primary Objective and Endpoint Primary Objective
Exploration of phenotypic heterogeneity in patients with ASD
Primary endpoint
Routine Care Clinical Investigation Criteria
Scores on assessment scales
In 5-40 of cases genetic factors are identified as the cause of these disorders
Despite this unique definition and the advancement of techniques ASD is still a clinically and genetically heterogeneous condition as several hundred genes have been identified to date
Primary Objective and Endpoint Primary Objective
Exploration of phenotypic heterogeneity in patients with ASD
Primary endpoint
Routine Care Clinical Investigation Criteria
Scores on assessment scales
Detailed Description:
Autism Spectrum Disorders ASD are a heterogeneous and severe developmental abnormalities of the nervous system characterized by deficits affecting social interactions and verbal and nonverbal communication DSM-5 2013 affecting approximately 1 of the general population Brugha 2012 In 5-40 of cases genetic factors are identified as the cause of these disorders prevalence depending on the technique used Exome andor SNPs Array and the associated intellectual deficit In the majority of cases the etiology remains unknown The familial aggregation of ASDs and the significant excess of concordant monozygotic twins over dizygotic twins demonstrate the strong involvement of genetic factors in autism Studies of microdeletionsmicroduplications copy number variants or by Whole Exome Sequencing and Whole Genome Sequencing Single Nucleotide Variants show the involvement of many genes in the predisposition to autism However ASD remains a clinically and genetically heterogeneous disorder since several hundred genes have been identified to date
The main objective of our project is to allow the retrospective and prospective collection of data on the phenotypic and genetic characterization of ASD patients in a structured way in order to allow the development of a new dynamic in terms of research The identification of genetic factors Delorme et al Nature Medicine 2013 and biological pathways involved in the emergence of autistic symptoms Bourgeron Nature Neuroscience 2015 is fundamental The identification of biological pathways is an indispensable step for the development of new therapeutic strategies In addition a major challenge of this study is to better understand the phenotypegenotype relationships in ASD This requires the constitution of a large cohort of patients taking into account their multimodal extensive and precise exploration of clinical neuroanatomical MRI EEG and biological phenotypes and to correlate them with genetic data
The work carried out by our teams and collaborators has led to the identification of numerous genes associated with ASD and involved in synaptic formation and regulation NLGN3-4 Jamain et al Nature Genetics 2003 SHANK1-3 Durand el al Nature Genetics 2007 Sato et al Am J Hum Genet 2013 Leblond et al Plos Genetics 2013 2014 CNTN-6 Mercati et al Mol Psychiatry 2016 and CNTNAP4 Karayannis Nature 2014 for review Toro et al TIGS 2012 Delorme et al Nature Medicine 2013 Bourgeron Nature Neuroscience 2015 This work was combined with extensive phenotypic explorations of patients and their relatives It has allowed us to specify the neuroanatomical characteristics of the patients Lefebvre et al Biol Psychiatry 2014 and their genetic substrate Toro et al Mol Psychiatry 2015 but also the underlying cognitive processes Dumas et al PNAS 2014 Zalla et al Cortex 2014 2015 Grezes et al Hum Brain Mapp 2014 More recently we have shown the existence of abnormalities in the regulation of the melatonin synthesis pathway Pagan et al TransPsychiatry 2014 Pagan et al J pineal Res 2015 or immunological abnormalities in particular HLA anomalies Bennabi et al 2018
Description of the population to be studied and rationale for its choice
We wish to explore the heterogeneity of autism spectrum disorders in a population received in routine care in our evaluation units These are patients followed in the Child and Adolescent Psychiatry Department at the Robert Debré Hospital in Paris who meet the diagnostic criteria of ASD according to DSM-5 aged 0 to 17 years
Description of the elements on which the research focuses
The main objective of our project is to explore the phenotypic heterogeneity of ASD The collection of data from the routine clinical evaluation of a large number of subjects will allow for a better phenotypic and genetic characterization of patients in a structured manner to allow for the development of a new dynamic in terms of research We wish to carry out a non-interventional mono-centric study based on data from the evaluation of patients in clinical practice
To allow this work we must favour
1 the collection of phenotypic data of the patients evaluated in our service including
Clinical phenotypes standardized evaluation of phenotypes in clinical practice according to current recommendations
Neuroanatomical phenotypes brain imaging MRI electrophysiology EEG Eye-Tracking
Biological phenotypes serological genetic of patients hospitalized in our department
2 the linking of these data via a database regrouping this information or allowing them to be grouped
3 the development of a new dynamic in terms of translational research concerning ASD
The creation of this cohort based on data from the evaluation done in clinical practice will help identify biological pathways involved in autism the development of new therapeutic strategies for patients and a more personalized medicine
Justification of the duration of the research
The total duration of the research will be 6 years 5 years of inclusion and a maximum of 12 months of patient observation renewable by possible extension of the study
This duration will allow the collection of data from the evaluation of approximately 300 patients per year ie 1500 patients over the next 5 years This study duration is essential to collect a sufficient number of patients to have enough statistical power for the study Also the extensive phenotypic and genetic exploration requires - in order to be able to cross-reference the data and establish relevant subgroups - to have large samples of subjects
The main objective of our project is to allow the retrospective and prospective collection of data on the phenotypic and genetic characterization of ASD patients in a structured way in order to allow the development of a new dynamic in terms of research The identification of genetic factors Delorme et al Nature Medicine 2013 and biological pathways involved in the emergence of autistic symptoms Bourgeron Nature Neuroscience 2015 is fundamental The identification of biological pathways is an indispensable step for the development of new therapeutic strategies In addition a major challenge of this study is to better understand the phenotypegenotype relationships in ASD This requires the constitution of a large cohort of patients taking into account their multimodal extensive and precise exploration of clinical neuroanatomical MRI EEG and biological phenotypes and to correlate them with genetic data
The work carried out by our teams and collaborators has led to the identification of numerous genes associated with ASD and involved in synaptic formation and regulation NLGN3-4 Jamain et al Nature Genetics 2003 SHANK1-3 Durand el al Nature Genetics 2007 Sato et al Am J Hum Genet 2013 Leblond et al Plos Genetics 2013 2014 CNTN-6 Mercati et al Mol Psychiatry 2016 and CNTNAP4 Karayannis Nature 2014 for review Toro et al TIGS 2012 Delorme et al Nature Medicine 2013 Bourgeron Nature Neuroscience 2015 This work was combined with extensive phenotypic explorations of patients and their relatives It has allowed us to specify the neuroanatomical characteristics of the patients Lefebvre et al Biol Psychiatry 2014 and their genetic substrate Toro et al Mol Psychiatry 2015 but also the underlying cognitive processes Dumas et al PNAS 2014 Zalla et al Cortex 2014 2015 Grezes et al Hum Brain Mapp 2014 More recently we have shown the existence of abnormalities in the regulation of the melatonin synthesis pathway Pagan et al TransPsychiatry 2014 Pagan et al J pineal Res 2015 or immunological abnormalities in particular HLA anomalies Bennabi et al 2018
Description of the population to be studied and rationale for its choice
We wish to explore the heterogeneity of autism spectrum disorders in a population received in routine care in our evaluation units These are patients followed in the Child and Adolescent Psychiatry Department at the Robert Debré Hospital in Paris who meet the diagnostic criteria of ASD according to DSM-5 aged 0 to 17 years
Description of the elements on which the research focuses
The main objective of our project is to explore the phenotypic heterogeneity of ASD The collection of data from the routine clinical evaluation of a large number of subjects will allow for a better phenotypic and genetic characterization of patients in a structured manner to allow for the development of a new dynamic in terms of research We wish to carry out a non-interventional mono-centric study based on data from the evaluation of patients in clinical practice
To allow this work we must favour
1 the collection of phenotypic data of the patients evaluated in our service including
Clinical phenotypes standardized evaluation of phenotypes in clinical practice according to current recommendations
Neuroanatomical phenotypes brain imaging MRI electrophysiology EEG Eye-Tracking
Biological phenotypes serological genetic of patients hospitalized in our department
2 the linking of these data via a database regrouping this information or allowing them to be grouped
3 the development of a new dynamic in terms of translational research concerning ASD
The creation of this cohort based on data from the evaluation done in clinical practice will help identify biological pathways involved in autism the development of new therapeutic strategies for patients and a more personalized medicine
Justification of the duration of the research
The total duration of the research will be 6 years 5 years of inclusion and a maximum of 12 months of patient observation renewable by possible extension of the study
This duration will allow the collection of data from the evaluation of approximately 300 patients per year ie 1500 patients over the next 5 years This study duration is essential to collect a sufficient number of patients to have enough statistical power for the study Also the extensive phenotypic and genetic exploration requires - in order to be able to cross-reference the data and establish relevant subgroups - to have large samples of subjects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None