Predict to Prevent Frontotemporal Lobar Degeneration (FDT) and Amyotrophic Lateral Sclerosis (ALS) (PREV-DEMALS)
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|ClinicalTrials.gov Identifier: NCT02590276|
Recruitment Status : Completed
First Posted : October 29, 2015
Last Update Posted : January 20, 2021
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 Alzheimer's 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:
- TDP-43 aggregates in neurons and
- 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-TDP/FTD-tau) in patients that will be eligible for trials targeting specific pathological lesion.
|Condition or disease||Intervention/treatment||Phase|
|Frontotemporal Lobar Degeneration Amyotrophic Lateral Sclerosis||Behavioral: characterization||Not Applicable|
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
- 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.
- 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 (BrainVISA/Morphologist software).
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis|
|Actual Study Start Date :||October 8, 2015|
|Actual Primary Completion Date :||October 27, 2020|
|Actual Study Completion Date :||October 27, 2020|
- Change in behavioral assessment (20 scales) [ Time Frame: at baseline, 16 weeks and 32weeks ]
- Change in MRI morphological criteria [ Time Frame: at baseline, 16 weeks and 32weeks ]
- Change in cerebral perfusion by SPECT / PET [ Time Frame: at baseline, 16 weeks and 32weeks ]
- correlations between behavioral assessment, MRI morphological criteria, Cerebral perfusion and metabolism by SPECT / PET and transcriptome analysis [ Time Frame: 32 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02590276
|Groupe Hospitalier Pitié-Salpêtrière - Charles Foix|
|Paris, France, 75013|
|Principal Investigator:||LE BER Isabelle, MD, PhD||Assistance Publique - Hôpitaux de Paris|