Natural History Characterization in Symptomatic and Asymptomatic Progranuline Gene Mutation Carriers
NCT ID: NCT04014673
Last Updated: 2024-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
78 participants
INTERVENTIONAL
2010-01-19
2022-10-06
Brief Summary
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Detailed Description
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FTD is difficult to detect at an early stage, and no clinical, biological or imaging features can predict the underlying pathology in living patients. Therapeutic perspectives have emerged against tau aggregation, PGRN deficit and C9orf72 expansion. Presymptomatic carriers of genetic FTD would benefit, before onset of symptoms, from these therapeutics that would delay or prevent the disease. At this step, it becomes crucial to develop markers to know how many years before symptoms, the pathological process begins, to treat the patients at the earliest 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. 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. Ninety participants including 8 patients and 82 'at-risk' individuals will be recruited and evaluated by clinical partners of the project (Paris, Lille, Rouen, Toulouse, Saint-Etienne, Marseille, Nantes). 'At-risk individuals' are the first- degree relatives of PGRN patients, who have a high a risk (50%) to carry the mutation.
Brain structural changes will be evaluated by voxel-based morphometry (SPM12 software) to assess global brain atrophy in one with the evaluation of atypical shape patterns such as cortical thickness (Freesurfer software) and the study of the cortical sulci (BrainVISA/Morphologist software).
Fluoro Deoxy DGlucose-Positron Emission Tomography (FDG-PET) will allow the identification of brain metabolic markers. Then voxel-based methods using Statistical Parametric Mapping software will be applied to compare different groups or analyze correlations between brain metabolism and cognitive deficits.
The identification of peripheral biomarkers of disease onset and disease progression will take advantage from RNA sequencing, in order to study gene expression and RNA splicing alterations in lymphocytes of patients and 'at risk individuals'.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
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Patients with a PGRN gene mutation
Symptomatic patients with a PGRN gene mutation
Behavioral : Characterization
Behavioral scales and neuropsychological tests; MRI, SPECT/PET
Presymptomatic individuals
Asymptomatic 'At-risk' individuals with a PGRN gene mutation
Behavioral : Characterization
Behavioral scales and neuropsychological tests; MRI, SPECT/PET
healthy volunteers
'At-risk' individuals without a PGRN gene mutation
Behavioral : Characterization
Behavioral scales and neuropsychological tests; MRI, SPECT/PET
Interventions
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Behavioral : Characterization
Behavioral scales and neuropsychological tests; MRI, SPECT/PET
Eligibility Criteria
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Inclusion Criteria
* Signed informed consent for genetic and clinical study
* To be carrier of a PGRN mutation - Diagnosis criteria of FTD
* To be affiliated to the social security scheme
* Age ≥ 18
* To be first degree relative of a person carrying a PGRN mutation or first degree relative of FTD deceased patient whose PGRN mutation as been identified in the family
* Signed informed consent for genetic and clinical study
* To be affiliated to the social security scheme
Exclusion Criteria
* Breastfeeding and pregnant women
* Presence of another intercurrent neurological pathology (vascular cerebral accident, tumor, etc.....)
* Presence of neurological or neurodegenerative disease
* Clinical proven signs of FTD, language disorder, praxis disorder, mnemic, of parkinson's syndrome or amyotrophic lateral sclerosis
* Contra-indication to perform a brain MRI and/or PET-FDG
* Inability to lie one hour without moving
* Breastfeeding and pregnant women
* Severe vascular lesion , tumor or infectious brain imaging if an MRI was done previously
18 Years
ALL
Yes
Sponsors
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Assistance Publique - Hôpitaux de Paris
OTHER
Responsible Party
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Principal Investigators
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Isabelle LE BER, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Assistance Publique - Hôpitaux de Paris
Locations
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Groupe Hospitalier Pitié-Salpêtrière - Charles Foix
Paris, , France
Pitié Salpetriere Hospital
Paris, , France
Countries
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References
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Caroppo P, Habert MO, Durrleman S, Funkiewiez A, Perlbarg V, Hahn V, Bertin H, Gaubert M, Routier A, Hannequin D, Deramecourt V, Pasquier F, Rivaud-Pechoux S, Vercelletto M, Edouart G, Valabregue R, Lejeune P, Didic M, Corvol JC, Benali H, Lehericy S, Dubois B, Colliot O, Brice A, Le Ber I; Predict-PGRN study group. Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease? J Alzheimers Dis. 2015;47(3):751-9. doi: 10.3233/JAD-150270.
Saracino D, Sellami L, Boniface H, Houot M, Pelegrini-Issac M, Funkiewiez A, Rinaldi D, Locatelli M, Azuar C, Causse-Lemercier V, Jaillard A, Pasquier F, Chastan M, Wallon D, Hitzel A, Pariente J, Pallardy A, Boutoleau-Bretonniere C, Guedj E, Didic M, Migliaccio R, Kas A, Habert MO, Le Ber I; Predict-PGRN. Brain Metabolic Profile in Presymptomatic GRN Carriers Throughout a 5-Year Follow-up. Neurology. 2023 Jan 24;100(4):e396-e407. doi: 10.1212/WNL.0000000000201439. Epub 2022 Oct 18.
Saracino D, Dorgham K, Camuzat A, Rinaldi D, Rametti-Lacroux A, Houot M, Clot F, Martin-Hardy P, Jornea L, Azuar C, Migliaccio R, Pasquier F, Couratier P, Auriacombe S, Sauvee M, Boutoleau-Bretonniere C, Pariente J, Didic M, Hannequin D, Wallon D; French Research Network on FTD/FTD-ALS; PREV-DEMALS and Predict-PGRN study groups; Colliot O, Dubois B, Brice A, Levy R, Forlani S, Le Ber I. Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications. J Neurol Neurosurg Psychiatry. 2021 Dec;92(12):1278-1288. doi: 10.1136/jnnp-2021-326914. Epub 2021 Aug 4.
Other Identifiers
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P071229
Identifier Type: -
Identifier Source: org_study_id