Natural History Characterization in Symptomatic and Asymptomatic Progranuline Gene Mutation Carriers

NCT04014673 | Completed

• 1 other identifier: P071229
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to investigate whether cognitive deficits, structural and functional changes can be detected before symptom onset in presymptomatic progranuline mutation carriers. 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.

Conditions

Frontotemporal Lobar Degeneration

Keywords

Frontotemporal Dementia,; biomarkers,; brain Imaging PET

Outcome Measures

Primary Outcomes (12)

• Rate of change of Frontal Assessment Battery score (/18)

  Executive functions changes over time (rate of change in neuropsychological test)

  at baseline 0 Months,at 42 Months,at 72 Months

• Rate of change of Trail Making Test B-A time (seconds)

  Cognitive flexibility changes over time (rate of change in neuropsychological test)

  at baseline 0 Months,at 42 Months,at 72 Months

• Rate of change of Ekman's faces test score (/35)

  Emotional assessment changes over time (rate of change in neuropsychological test)

  at baseline 0 Months,at 42 Months,at 72 Months

• Rate of change of Faux-pas test score (/35)

  Social cognition changes over time (rate of change in neuropsychological test)

  at baseline 0 Months,at 42 Months,at 72 Months

• Rate of change of Digit span score

  Short-term memory changes over time (rate of change in neuropsychological test)

  at baseline 0 Months,at 42 Months,at 72 Months

• Rate of change of Free and Cued Selective Reminding test, total recall score (/48)

  Long-term memory changes over time (rate of change in neuropsychological test)

  at baseline 0 Months,at 42 Months,at 72 Months

• Rate of change of Boston Naming test score (/34)

  Language changes over time (rate of change in neuropsychological test)

  at baseline 0 Months,at 42 Months,at 72 Months

• Rate of change of Gestural Praxis battery score (/168)

  Gestural praxis changes over time (rate of change in neuropsychological test)

  at baseline 0 Months,at 42 Months, at 72 Months

• Rate of change of Neuropsychiatric Inventory score (/144)

  Behavioral changes over time (rate of change in neuropsychological questionnaire)

  at baseline 0 Months,at 42 Months,at 72 Months

• Rate of change of Apathy Evaluation Scale score (/42)

  Apathy changes over time (rate of change in neuropsychological questionnaire)

  at baseline 0 Months,at 42 Months,at 72 Months

• Change in MRI morphological criteria (brain atrophy by voxel-based morphometry)

  at baseline 0 Months,at 42 Months,at 72 Months

• Change in cerebral metabolism by PET (metabolic markers by Fluoro-DeoxyDGlucose-Positron Emission Tomography (FDG-PET))

  at baseline 0 Months,at 42 Months,at 72 Months

Secondary Outcomes (2)

• Correlations between cognitive and behavioral scores, MRI morphological criteria, cerebral metabolism by FDG-PET and transcriptome analysis in presymptomatic subjects and in symptomatic patients at early disease stage

  at baseline 0 Months,at 42 Months,at 72 Months

• Differences in transcriptome analysis between symptomatic patients, asymptomatic carriers and controls.

  at baseline 0 Months,at 42 Months,at 72 Months

Study Arms (3)

Patients with a PGRN gene mutation

OTHER

Symptomatic patients with a PGRN gene mutation

Behavioral: Behavioral : Characterization

Presymptomatic individuals

OTHER

Asymptomatic 'At-risk' individuals with a PGRN gene mutation

Behavioral: Behavioral : Characterization

healthy volunteers

OTHER

'At-risk' individuals without a PGRN gene mutation

Behavioral: Behavioral : Characterization

Interventions

Behavioral : Characterization BEHAVIORAL

Behavioral scales and neuropsychological tests; MRI, SPECT/PET

Patients with a PGRN gene mutation; Presymptomatic individuals; healthy volunteers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18
• 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

You may not qualify if:

• Inability to lie one hour without moving
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Groupe Hospitalier Pitié-Salpêtrière - Charles Foix

Paris, 75013, France

Location

Pitié Salpetriere Hospital

Paris, 75013, France

Location

Related Publications (3)

• 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.

  PMID: 26401709 BACKGROUND

• 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.

  PMID: 36257714 RESULT

• 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.

  PMID: 34349004 DERIVED

MeSH Terms

Conditions

Frontotemporal Lobar Degeneration; Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Isabelle LE BER, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: July 10, 2019
• Study Start: January 19, 2010
• Primary Completion: October 6, 2022
• Study Completion: October 6, 2022
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)