Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06595212
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-11
Brief Title:
Genetics and Environment INtersection in the ALS-FTD Spectrum an Italian Twins Cohort StudY with a Multi-Omics Approach
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Genetics and Environment INtersection in the Amyotrophic Lateral Sclerosis - FrontoTemporal Dementia Spectrum an Italian Twins Cohort StudY with a Multi-Omics Approach
Status:
RECRUITING
Status Verified Date:
2024-09
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:
GENIALITY
Brief Summary:
The goal of this study is to learn from discordant twins affected by Amyotrophic Lateral Sclerosis andor Frontotemporal Dementia the contribution of genetic background versus environmental exposure The main questions it aims to answer is
How far does the genetic background explain the onset of ALSFTD in discordant twins
Which environmental factors and events occurring in post-fetal life influence the onset or progression of this neurodegenerative condition Participants with ALS andor FTD with a monozygotic or dizygotic twin willing to contribute to this research will be followed up for two years by specialized Motor Neuron Disorders centers in Italy donating biological specimen for -omic sciences analysis and checking out if prodromal signssymptoms of these two conditions will develop during time
How far does the genetic background explain the onset of ALSFTD in discordant twins
Which environmental factors and events occurring in post-fetal life influence the onset or progression of this neurodegenerative condition Participants with ALS andor FTD with a monozygotic or dizygotic twin willing to contribute to this research will be followed up for two years by specialized Motor Neuron Disorders centers in Italy donating biological specimen for -omic sciences analysis and checking out if prodromal signssymptoms of these two conditions will develop during time
Detailed Description:
The main objective of the study is to develop a prospective national twins cohort and virtual biobank collecting demographic clinical and instrumental data and biological samples of twins with ALSFTD Through the definition of a multi-omics profile in ALS twins the study aims to disclose the burden of environmental or genetic risk factors for ALSFTD and ALS specific biological signatures Secondary aims include
to disclose part of the heritability gap in monozygotic MZ discordant twins
to assess the burden of epigenetic and transcriptomic differences between MZ discordant twins uncovering which pathways are activatedinactivated in asymptomatic twins and may protect them from the neurodegenerative process
to evaluate the effects of environment on the risk of developing ALSFTD discordant twins and of developing different phenotypes of ALS concordant twins Exposure history will be related to quantification of pesticides heavy metals and metalloids in biological samples
to investigate how lifetime environmental exposures affect microbiota composition and next metabolomics and immune profile
to correlate biological signatures with clinical features and disease heterogeneity onset progression survival for discordant twins
to correlate environmental factors exposure with biological factors as mentioned above egmicrobiota immunological factors
to acquire biological data over time to discriminate between changes related to disease pathogenesis and epiphenomena secondary to the disease advancement
to assess neurophysiological neuropsychological and imaging signatures within the ALS-FTD spectrum of disease across discordant twins in particular in the asymptomatic twin in order to disclose potential presymptomatic subclinical traits In concordant twins the same extensive batteries will be used to evaluate whether disease progression proceeds at the same pace or affects similar or divergent neuroanatomical substrates
Study population Being a national ALS-FTD twin cohort study study population could include all Italian MZ and dizygotic DZ twins of whom at least one is affected by ALS or ALS-FTD and possibly their parents for trios studies ALSFTD twins will be invited from the referring neurologist to participate in the GENIALITY study and will be sent for screening and baseline visits to the nearest clinical center involved in this study either Modena Turin or Palermo
Twin pairs will undergo a detailed interview visit clinical tests including neuropsychological testing NPS neuroimaging and neurophysiological studies extensive environmental and exposure history and blood CSF optional skin hair saliva and stool collection
ALS patients will be followed up by the centers with visits scheduled every 3-4 months as for clinical practice while healthy twins will be asked to be followed with neurological evaluations every 6 months up to 24 months of the study duration
Twins and parents optional will be asked to undergo a detailed interview neurological examination samples collection parent-offspring trios studies including blood sample saliva and faeces una tantum
Standard Operating Procedures SOPs for sampling biobanking clinical and imaging studies will be shared by all the centers involved in the consortium SOPs will include requirements for collection analysis and storage of biological materials and guidelines concerning the shipping of the samples from one center to another but also guideline concerning the patients recruitment informed consent collection clinical scales questionnaires administration Furthermore a battery of NPS tests will be shared with centers as well as methods for neurophysiological assessment and requirements for imaging studies brain MRI and PET
This project will generate multi-omics parameters and correlated demographic and clinical data in ALSFTD patients their co-twins and possibly their parents Data collected from interviewers medical record review and laboratory data will be recorded in online case report forms
to disclose part of the heritability gap in monozygotic MZ discordant twins
to assess the burden of epigenetic and transcriptomic differences between MZ discordant twins uncovering which pathways are activatedinactivated in asymptomatic twins and may protect them from the neurodegenerative process
to evaluate the effects of environment on the risk of developing ALSFTD discordant twins and of developing different phenotypes of ALS concordant twins Exposure history will be related to quantification of pesticides heavy metals and metalloids in biological samples
to investigate how lifetime environmental exposures affect microbiota composition and next metabolomics and immune profile
to correlate biological signatures with clinical features and disease heterogeneity onset progression survival for discordant twins
to correlate environmental factors exposure with biological factors as mentioned above egmicrobiota immunological factors
to acquire biological data over time to discriminate between changes related to disease pathogenesis and epiphenomena secondary to the disease advancement
to assess neurophysiological neuropsychological and imaging signatures within the ALS-FTD spectrum of disease across discordant twins in particular in the asymptomatic twin in order to disclose potential presymptomatic subclinical traits In concordant twins the same extensive batteries will be used to evaluate whether disease progression proceeds at the same pace or affects similar or divergent neuroanatomical substrates
Study population Being a national ALS-FTD twin cohort study study population could include all Italian MZ and dizygotic DZ twins of whom at least one is affected by ALS or ALS-FTD and possibly their parents for trios studies ALSFTD twins will be invited from the referring neurologist to participate in the GENIALITY study and will be sent for screening and baseline visits to the nearest clinical center involved in this study either Modena Turin or Palermo
Twin pairs will undergo a detailed interview visit clinical tests including neuropsychological testing NPS neuroimaging and neurophysiological studies extensive environmental and exposure history and blood CSF optional skin hair saliva and stool collection
ALS patients will be followed up by the centers with visits scheduled every 3-4 months as for clinical practice while healthy twins will be asked to be followed with neurological evaluations every 6 months up to 24 months of the study duration
Twins and parents optional will be asked to undergo a detailed interview neurological examination samples collection parent-offspring trios studies including blood sample saliva and faeces una tantum
Standard Operating Procedures SOPs for sampling biobanking clinical and imaging studies will be shared by all the centers involved in the consortium SOPs will include requirements for collection analysis and storage of biological materials and guidelines concerning the shipping of the samples from one center to another but also guideline concerning the patients recruitment informed consent collection clinical scales questionnaires administration Furthermore a battery of NPS tests will be shared with centers as well as methods for neurophysiological assessment and requirements for imaging studies brain MRI and PET
This project will generate multi-omics parameters and correlated demographic and clinical data in ALSFTD patients their co-twins and possibly their parents Data collected from interviewers medical record review and laboratory data will be recorded in online case report forms
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