Early Biomarkers of Neurodegeneration in Parkinsonian Syndromes: Analysis in Very High Field (7T) Brain MRI.

Assistance Publique Hopitaux De Marseille6 sites in 1 country63 target enrollmentJanuary 15, 2024

ConditionsParkinson Disease Progressive Supranuclear Palsy

Overview

Phase: N/A
Intervention: Not specified
Conditions: Parkinson Disease
Sponsor: Assistance Publique Hopitaux De Marseille
Enrollment: 63
Locations: 6
Primary Endpoint: Sodium accumulation between Parkinson disease patients and Progressive Supranuclear Palsy
Status: Not Yet Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

January 15, 2024

End Date

January 15, 2028

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Assistance Publique Hopitaux De Marseille

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

•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.
•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.
•Claustrophobia or any other condition preventing full MRI.
•Montreal Cognitive Assessment (MOCA) test \< 25/30
•Pregnant or breast-feeding woman or protected person (under guardianship, curatorship, deprived of liberty).
•For Progressive Supra-nuclear Palsy:
•Inclusion criteria:
•Patients aged 40 to 80
•Fulfilling the diagnostic criteria for soPSP (Höglinger et al., 2017) :
•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

Outcomes

Primary Outcomes

Sodium accumulation between Parkinson disease patients and Progressive Supranuclear Palsy

Time Frame: Between month 0 and month 3 after inclusion

Comparison of intracerebral sodium accumulation measured by very high-field (7T) cerebral MRI between subjects with Idiopathic Parkinson's Disease and subjects with early-stage Progressive Supra-Nuclear Palsy

Secondary Outcomes

Brain atrophy between MPI and control group(Between month 0 and month 3 after inclusion)
Sodium accumulation between Progressive Supra-nuclear patients (soPSP) and control subjects(Between month 0 and month 3 after inclusion)
Brain atrophy between MPI and soPSP patients(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and Hospital Anxiety and Depression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and Sleep Behavior Disorder(Between month 0 and month 3 after inclusion)
Iron accumulation between soPSP and control group(Between month 0 and month 3 after inclusion)
Accumulation of neuromelanin between soPSP patients and control group(Between month 0 and month 3 after inclusion)
Movement of water molecules between MPI patients and control group(Between month 0 and month 3 after inclusion)
Structural connectivity between MPI and soPSP patients(Between month 0 and month 3 after inclusion)
Structural connectivity between soPSP patients and control group(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and sense of smell(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and severity of disease(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and Hospital Anxiety and Depression(Between month 0 and month 3 after inclusion)
Sodium accumulation between Parkinson disease patients (MPI) and control subjects(Between month 0 and month 3 after inclusion)
Iron accumulation between soPSP patients and control group(Between month 0 and month 3 after inclusion)
Structural connectivity between MPI patients and control group(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and age(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and laterality(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and laterality(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and age(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and age(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and duration of disease progression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and severity of disease(Between month 0 and month 3 after inclusion)
Brain atrophy between soPSP and control group(Between month 0 and month 3 after inclusion)
Movement of water molecules between MPI and soPSP patients(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and age(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and sex(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and laterality(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and duration of disease progression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and duration of disease progression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and duration of disease progression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and sense of smell(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and quality of life(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and quality of life(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and quality of life(Between month 0 and month 3 after inclusion)
Accumulation of neuromelanin between MPI patients and control group(Between month 0 and month 3 after inclusion)
Movement of water molecules between soPSP patients and control group(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and age(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and sex(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and laterality(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and sex(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and laterality(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and sense of smell(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and quality of life(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and Hospital Anxiety and Depression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and non-motor fluctuations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and non-motor fluctuations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and hypotension(Between month 0 and month 3 after inclusion)
Iron accumulation between MPI and soPSP patients(Between month 0 and month 3 after inclusion)
Accumulation of neuromelanin between MPI and soPSP patients(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and sex(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and sex(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and duration of disease progression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and sense of smell(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and sense of smell(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and quality of life(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and Hospital Anxiety and Depression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and motivation scale(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and severity of disease(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and severity of disease(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and Sleep Behavior Disorder(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and motivation scale(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and motivation scale(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and motivation scale(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and non-motor fluctuations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and cognitives functions(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and cognitives functions(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and hallucinations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and hallucinations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and hallucinations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and Hospital Anxiety and Depression(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and Sleep Behavior Disorder(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and Sleep Behavior Disorder(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and non-motor fluctuations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and hypotension(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and hypotension(Between month 0 and month 3 after inclusion)
Measurement of the dependency between accumulation of neuromelanin and hypotension(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and Sleep Behavior Disorder(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and motivation scale(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and non-motor fluctuations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and hallucinations(Between month 0 and month 3 after inclusion)
Measurement of the dependency between brain atrophy and cognitives functions(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and cognitives functions(Between month 0 and month 3 after inclusion)
Measurement of the dependency between structural connectivity and cognitives functions(Between month 0 and month 3 after inclusion)
Measurement of the dependency between iron accumulation and hypotension(Between month 0 and month 3 after inclusion)
Measurement of the dependency between sodium accumulation and hallucinations(Between month 0 and month 3 after inclusion)