Ignite Creation Date:
2024-05-06 @ 7:44 AM
Last Modification Date:
2024-10-26 @ 11:51 AM
Study NCT ID:
NCT02590276
Status:
COMPLETED
Last Update Posted:
2021-01-20
First Post:
2015-10-05
Brief Title:
Predict to Prevent Frontotemporal Lobar Degeneration FDT and Amyotrophic Lateral Sclerosis ALS
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Status:
COMPLETED
Status Verified Date:
2016-08
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:
PREV-DEMALS
Brief Summary:
The project focuses on C9orf72 the most frequent genetic form of frontotemporal dementias FTD or frontotemporal lobar degeneration FTLD and amyotrophic lateral sclerosis ALS FTD is the second commonest cause of degenerative dementia in presenium after Alzheimers disease Behavioural and cognitive impairments progressively lead to dementia ALS produces progressive muscle weakness leading to the death in 2 to 4 years Since 2006 major discoveries have linked FTLD and ALS
1 TDP-43 aggregates in neurons and
2 C9orf72 mutations is a major genetic cause in both disorders
Two major pathological subtypes are now defined in FTD FTD-TDP and FTD-TAU C9orf72 mutations associated to FTD-TDP are the most frequent genetic causes of FTD 15 FTD-ALS 65 and ALS 40
FTD is difficult at an early stage and no clinical biological or imaging features can predict the underlying pathology in living patients Therapeutic perspectives emerged against tau aggregation progranulin deficit and C9orf72 expansion antisense Presymptomatic carriers of genetic FTD would benefit before onset of symptoms from these therapeutic that would delay or prevent the disease At this step it becomes crucial to develop markers to know how many years before symptoms does the pathological progress begin to treat the patients at the most early stage of the disease Markers are also needed to predict the pathology FTD-TDPFTD-tau in patients that will be eligible for trials targeting specific pathological lesion
1 TDP-43 aggregates in neurons and
2 C9orf72 mutations is a major genetic cause in both disorders
Two major pathological subtypes are now defined in FTD FTD-TDP and FTD-TAU C9orf72 mutations associated to FTD-TDP are the most frequent genetic causes of FTD 15 FTD-ALS 65 and ALS 40
FTD is difficult at an early stage and no clinical biological or imaging features can predict the underlying pathology in living patients Therapeutic perspectives emerged against tau aggregation progranulin deficit and C9orf72 expansion antisense Presymptomatic carriers of genetic FTD would benefit before onset of symptoms from these therapeutic that would delay or prevent the disease At this step it becomes crucial to develop markers to know how many years before symptoms does the pathological progress begin to treat the patients at the most early stage of the disease Markers are also needed to predict the pathology FTD-TDPFTD-tau in patients that will be eligible for trials targeting specific pathological lesion
Detailed Description:
This study will investigate whether cognitive deficits structural and functional changes can be detected before symptom onset in presymptomatic mutation carrier The main objectives of the project are to identify novel cognitive brain imaging markers and peripheral biomarkers for early diagnosis of FTLD and to follow disease progression Methodology
1 Recruitment and evaluation of participants neurological behaviour and cognition evaluations One hundred participants including 20 C9orf72 patients and 80 a-risk individuals will be recruited and evaluated by clinical partners of the project Paris Lille Limoges Rouen At-risk individuals are the first degree relatives of C9ORF72 patients who have a high a risk 50 to carry the mutation
2 Identifying brain structural markers Brain structural changes will be evaluated by voxel-based morphometry SPM12 software to assess global brain atrophy and evaluation of atypical shape patterns such as cortical thickness Freesurfer software and study of the cortical sulci BrainVISAMorphologist software
3 Identifying brain metabolic markers by Fluoro Deoxy DGlucose-Positron Emission Tomography FDG-PET We will apply voxel-based methods using Statistical Parametric Mapping software SPM8 to compare different groups or analyze correlations between brain metabolism and cognitive deficits
4 Identifying peripheral biomarkers of disease onset and disease progression We propose to use RNA sequencing to study gene expression and RNA splicing alterations in lymphocytes of C9ORF72 patients and at risk individuals
1 Recruitment and evaluation of participants neurological behaviour and cognition evaluations One hundred participants including 20 C9orf72 patients and 80 a-risk individuals will be recruited and evaluated by clinical partners of the project Paris Lille Limoges Rouen At-risk individuals are the first degree relatives of C9ORF72 patients who have a high a risk 50 to carry the mutation
2 Identifying brain structural markers Brain structural changes will be evaluated by voxel-based morphometry SPM12 software to assess global brain atrophy and evaluation of atypical shape patterns such as cortical thickness Freesurfer software and study of the cortical sulci BrainVISAMorphologist software
3 Identifying brain metabolic markers by Fluoro Deoxy DGlucose-Positron Emission Tomography FDG-PET We will apply voxel-based methods using Statistical Parametric Mapping software SPM8 to compare different groups or analyze correlations between brain metabolism and cognitive deficits
4 Identifying peripheral biomarkers of disease onset and disease progression We propose to use RNA sequencing to study gene expression and RNA splicing alterations in lymphocytes of C9ORF72 patients and at risk individuals
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| IDRCB 2015-A00856-43 | OTHER | ANSM | None |