Clinical trial NCT06155942: Early Biomarkers of Neurodegeneration in Parkinsonian Syndromes
Official title: Early Biomarkers of Neurodegeneration in Parkinsonian Syndromes: Analysis in Very High Field (7T) Brain MRI.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Parkinson Disease
Progressive Supranuclear Palsy
Keywords: MRI
Parkinson disease
progressive supranuclear palsy
biomarkers
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2023-12-05
Enrollment: 63
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Parkinson's disease (PD) is the most common degenerative Parkinson's syndrome and is linked, among other things, to the excessive accumulation of an abnormally aggregating protein, alpha-synuclein. Progressive Supranuclear Palsy (PSP) is another Parkinson's syndrome, linked, among other things, to the abnormal accumulation of the protein Tau, and expressed clinically by falls, early cognitive impairment and oculomotor disorders, not present in PD. The onset of these disorders is so gradual that differential diagnosis between the two diseases is only possible at a late stage, on average 3 to 5 years after the onset of symptoms.

To date, there is a lack of validated imaging biomarkers for diagnosing and monitoring PD and PSP. There is therefore an urgent need for the development of robust biomarkers capable of detecting neurodegeneration at an early stage, in order to aid differential diagnosis as soon as symptoms appear, and to potentially enable these patients to be included in specific therapeutic trials (as these diseases are pathophysiologically different) with potential neuroprotective effects.

The development of cutting-edge technologies such as 7T MRI, combined with optimized image processing methods, now enable non-invasive in vivo exploration and analysis of these small structures in terms of ion homeostasis (sodium), microstructure (volumetry, amount of iron and neuromelanin) and connectivity.


Eligibility criteria: For Parkinson Disease:

Inclusion Criteria:

1. Patients aged between 40 and 80
2. Fulfilling the diagnostic criteria for MPI (Postuma et al., 2015)
3. First motor symptom (rigidity, akinesia, tremor) less than 36 months ago
4. Patient entitled to or affiliated with a social security scheme
5. Patients who understood, completed and signed the consent form for study participation.

Exclusion Criteria:

1. Patient with a neurological disease of the central nervous system other than those studied (including history of stroke, repeated head trauma, documented encephalitis). In case of doubt, this criterion will be left to the discretion of the principal investigator, who is a neurologist.
2. Contraindications to 7T MRI: presence of an ocular metallic foreign body (accidental shrapnel or other), pacemaker (cardiac simulator) or neurostimulator (pain treatment), cochlear implants or any implanted electronic medical equipment in general, metallic heart valve, vascular clips implanted on a cranial aneurysm.
3. Claustrophobia or any other condition preventing full MRI.
4. Montreal Cognitive Assessment (MOCA) test \< 25/30
5. Pregnant or breast-feeding woman or protected person (under guardianship, curatorship, deprived of liberty).

For Progressive Supra-nuclear Palsy:

Inclusion criteria:

1. Patients aged 40 to 80
2. Fulfilling the diagnostic criteria for soPSP (Höglinger et al., 2017) :
3. First motor symptom (rigidity, akinesia, tremor) or falls or cognitive impairment (frontal syndrome or language disorder or cortico-basal syndrome) occurring less than 36 months ago
4. Patients benefiting from or affiliated to a social security scheme
5. Patients who have understood, completed and signed the study participation consent form

Exclusion criteria:

1. Patient with a neurological disease of the central nervous system other than those studied (including history of stroke, repeated head trauma, documented encephalitis). In case of doubt, this criterion will be left to the discretion of the principal investigator, who is a neurologist.
2. Contraindications to 7T MRI: presence of an ocular metallic foreign body (accidental shrapnel or other), pacemaker (cardiac simulator) or neurostimulator (pain treatment), cochlear implants or any implanted electronic medical equipment in general, metallic heart valve, vascular clips implanted on a cranial aneurysm.
3. Claustrophobia or any other condition preventing MRI.
4. Pregnant or breast-feeding woman or protected person (under guardianship, curatorship, deprived of liberty).

For Control group:

Inclusion criteria:

1. Subjects aged between 40 and 80
2. Subjects benefiting from or affiliated with a social security plan
3. Subjects who have understood, completed and signed the study participation consent form

Exclusion criteria:

1. Subjects with a known history of neurological disease of the central nervous system (e.g. Parkinson's disease, Alzheimer's, stroke, brain tumor, multiple sclerosis, amyotrophic lateral sclerosis, repeated head trauma, documented encephalitis, etc.). In case of doubt, this criterion will be left to the discretion of the principal investigator, who is a neurologist.
2. Contraindications to 7T MRI: presence of an ocular metallic foreign body (accidental shrapnel or other), pacemaker (cardiac simulator) or neurostimulator (pain treatment), cochlear implants or any implanted electronic medical equipment in general, metallic heart valve, vascular clips implanted on a cranial aneurysm.
3. Claustrophobia or any other condition preventing MRI.
4. Pregnant or breast-feeding women or protected persons (under guardianship, curatorship, deprived of liberty).

Primary outcomes:
measure: Sodium accumulation between Parkinson disease patients and Progressive Supranuclear Palsy
timeFrame: Between month 0 and month 3 after inclusion
Secondary outcomes:
measure: Sodium accumulation between Parkinson disease patients (MPI) and control subjects
timeFrame: Between month 0 and month 3 after inclusion
measure: Sodium accumulation between Progressive Supra-nuclear patients (soPSP) and control subjects
timeFrame: Between month 0 and month 3 after inclusion
measure: Brain atrophy between MPI and soPSP patients
timeFrame: Between month 0 and month 3 after inclusion
measure: Brain atrophy between MPI and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Brain atrophy between soPSP and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Iron accumulation between soPSP and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Iron accumulation between MPI and soPSP patients
timeFrame: Between month 0 and month 3 after inclusion
measure: Iron accumulation between soPSP patients and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Accumulation of neuromelanin between MPI and soPSP patients
timeFrame: Between month 0 and month 3 after inclusion
measure: Accumulation of neuromelanin between MPI patients and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Accumulation of neuromelanin between soPSP patients and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Movement of water molecules between MPI and soPSP patients
timeFrame: Between month 0 and month 3 after inclusion
measure: Movement of water molecules between MPI patients and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Movement of water molecules between soPSP patients and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Structural connectivity between MPI and soPSP patients
timeFrame: Between month 0 and month 3 after inclusion
measure: Structural connectivity between soPSP patients and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Structural connectivity between MPI patients and control group
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and age
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and sex
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and laterality
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and sex
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and age
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and laterality
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and age
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and sex
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and laterality
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and age
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and sex
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and laterality
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and age
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and sex
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and laterality
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and duration of disease progression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and duration of disease progression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and duration of disease progression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and duration of disease progression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and duration of disease progression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and sense of smell
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and sense of smell
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and sense of smell
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and sense of smell
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and sense of smell
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and severity of disease
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and severity of disease
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and severity of disease
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and severity of disease
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and Hospital Anxiety and Depression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and Hospital Anxiety and Depression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and Hospital Anxiety and Depression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and Hospital Anxiety and Depression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and Hospital Anxiety and Depression
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and Sleep Behavior Disorder
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and Sleep Behavior Disorder
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and Sleep Behavior Disorder
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and Sleep Behavior Disorder
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and Sleep Behavior Disorder
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and motivation scale
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and motivation scale
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and motivation scale
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and motivation scale
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and motivation scale
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and non-motor fluctuations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and non-motor fluctuations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and non-motor fluctuations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and non-motor fluctuations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and non-motor fluctuations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and cognitives functions
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and cognitives functions
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and cognitives functions
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and cognitives functions
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and cognitives functions
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and quality of life
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and hypotension
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and hypotension
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and hypotension
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and hypotension
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and hypotension
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between structural connectivity and hallucinations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between accumulation of neuromelanin and hallucinations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between iron accumulation and hallucinations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between brain atrophy and hallucinations
timeFrame: Between month 0 and month 3 after inclusion
measure: Measurement of the dependency between sodium accumulation and hallucinations
timeFrame: Between month 0 and month 3 after inclusion
Other outcomes:
Locations:
city: Aix-en-Provence
country: France
facility: Ch Pays D'Aix
city: Aubagne
country: France
facility: Hôpital Privé La Casamance - Service de Neurologie
city: Avignon
country: France
facility: Centre Hospitalier Avignon - Service de Neurologie
city: Nice
country: France
facility: CENTRE HOSPITALIER UNIVERSITAIRE NICE - Service de Neurologie
city: Nimes
country: France
facility: CENTRE HOSPITALIER NIMES - Service de Neurologie
city: Toulon
country: France
facility: CENTRE HOSPITALIER SAINTE MUSSE - Toulon
Study officials:
affiliation: AP-HM
name: Francois Cremieux
role: STUDY_DIRECTOR
References: