Multimodal Markers of Neurodegenerative Disorders at Presymptomatic Stages

Обзор

NeuroPrems is a prospective, monocentric, longitudinal, not relating to a medicinal product for human use, non-randomized, non-controlled research. The study mainly aims to identify longitudinal changes and events in multimodal markers of neurodegeneration and neuroinflammation during the presymptomatic phases of neurodegenerative diseases.

Вмешательства

• Лучевая терапия PET
  \[18F\]DPA-714 will be injected intravenously as a 1 minute intravenous bolus injection and dynamic PET acquisition will last 90 min. The aim is the quantification of the neuroimmune reaction during neuroinflammation process.
• Другое MRI 3T
  Brain MRI will aim at providing imaging biomarkers which will allow evaluating brain structure, microstructure, iron load, myelin, neurodegeneration of the substantia nigra and locus coeruleus, functional connectivity, brain perfusion and the glymphatic system.
• Другое Oculomotricity assessment
  Recording eye movements in a controlled environment (requiring no specific room or area) in binocular vision at a frequency \> 500Hz, while retaining infrared video footage of eye movements for high-quality clinical monitoring.
• Другое Magnetoencephalography assessment
  Recording brain magnetic activity using the Elekta Neuromag® TRIUX Magnetoencephalograph ; The participant will be comfortably seated in an adjustable-height chair. The device is enclosed in a shielded room isolated from external electric and magnetic fields to measure the extremely weak magnetic activities produced by the brain.
• Другое Body posture and gait assessment
  The acquisition of kinematic gait parameters will be achieved ; markers are positioned on the different segments of members, recognized by a camera system positioned on the walls. Neurophysiologic muscular activity of the lower limbs will also be recorded.
• Другое Voice recording
  Participants will be recorded during a single session at every visit upon baseline with a professional quality head mounted microphone.
• Другое Video-polysomnography
  Participants will complete standard sleep questionnaires before the visit and perform neurophysiological tests including cognitive tasks before and after the sleep recording.
• Биопрепарат Blood sampling, skin biopsy, excreta sampling, lumbar puncture
  Experimental analyses, genetic and multi-OMIC analyses for biomarker research.

Первичные конечные точки

• Rate of change of clinical, neurophysiological, anatomical and molecular marker profiles of neurodegenerescence and neuroinflammation in presymptomatic individuals [Срок оценки: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5]

Вторичные конечные точки (7)

• Intra-individual change in trajectory profiles determined by multimodal analysis [Срок оценки: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5]
• Rate and mean time to symptomatic conversion/progression [Срок оценки: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5]
• Mean time of onset in genetically presymptomatic individuals [Срок оценки: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5]
• Rate of change for each study marker [Срок оценки: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5]
• Rate of change in the self-administered questionnaires [Срок оценки: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5]
• Rate of change in consumption of information issued from Consultations, hospitalizations and medication prescriptions [Срок оценки: From Year -10 to Year 10 (annual update)]
• Time to loss of autonomy [Срок оценки: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5]

Критерии участия

• Inclusion Criteria :

• For all participants :

• Male or female
• Age ≥ 18 years
• Signed Informed consent by the subject
• Affiliated with a social security system or beneficiary of such a regime
• Ability to undergo an MRI exam with Gadobutrol
• For presymptomatic participants only :

• Absence of a diagnosis of neurodegenerative disease. And at least one of the criteria :
• Known carrier or relative of a patient carrying a mutation in a causal or at-risk responsible for a neurodegenerative disease
• Isolated REM sleep behavioral disorder
• Radiological isolated syndrome
• Abnormal brain protein aggregates
• For controls only :

• Absence of symptoms or diagnosis of neurodegenerative disease (or criteria corresponding to at risk group)
• Exclusion Criteria :

• Clinical symptoms fulfilling the criteria of a neurodegenerative disease (see table in criteria section)
• Refusal of blood draw or brain MRI
• MRI contraindication (see criteria section)
• Known allergy to gadoteric acid
• Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
• Pregnancy or breastfeeding. For women in fertile age a urine pregnancy test will be performed before the MRI.
• Inability to understand information about the protocol
• Person deprived of their liberty by judicial or administrative decision
• Person under legal protection (legal guardianship, tutelage or maintenance of justice)
• Person without any protection and unable to consent
• Other medical, neurological, psychiatric, or social conditions that in the investigator's opinion are likely to interfere with study conduct.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• Pitié Salpêtrière Hospital — Paris

Идентификаторы

NCT: NCT06516016 · 2024-A00824-43

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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