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Clinical Trial NCT07480187 for Parkinson Disease, Synucleinopathy, Alzheimer Disease is active, not recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here. | ||
Toward Molecular Profiling of Parkinson's Disease in Easily Accessible Biological Matrices 340 Non-Invasive Biomarker-Driven
Toward Molecular Profiling of Parkinson's Disease in Easily Accessible Biological Matrices
- PNRR-MAD-2022-12376035
CSF
plasma
skin
MRS
olfactory mucosa
| Participant Group/Arm | Intervention/Treatment |
|---|---|
Experimentalbiomarker analysis biomarker measurement in matched and unmatched biomatrices (blood, cerebrospinal fluid, skin biopses, brain metabolites by MRS, olfactory mucosa) collected by minimally-invasive procedures from patients with Parkinson's disease, Alzheimer's disease, and controls | biomarkers Comparison of biomarkers measured in matched and unmatched biomatrices (blood, cerebrospinal fluid, skin biopses, brain metabolites by MRS, olfactory mucosa) in patients with Parkinson's disease, Alzheimer's disease, and controls. These biomarkers include cerebrospinal fluid biomarkers of Alzheimer's disease, proximity-extension assay proteomic biomarkers, alpha-synuclein seed amplification assay performed in olfacto...Show More |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
clinical or CSF-based diagnosis | The clinical or cerebrospinal fluid (CSF)-based diagnosis will serve as the reference standard for the evaluation of biomarkers measured in blood, olfactory mucosa, and skin samples.
Clinical diagnosis will be established according to the diagnostic criteria described by Daniel M. Postuma and colleagues in the Movement Disorders criteria for prodromal Parkinson's disease (2015).
In participants undergoing lumbar puncture, CSF biomarkers including Aβ42/40 ratio, phosphorylated tau (p-tau181), and total tau (t-tau) will be measured to assess the presence of concomitant Alzheimer's disease pathology, using cut-off values established in previous international studies (e.g., Gobom et al., Clinical Chemistry and Laboratory Medicine, 2021).
In addition, CSF α-synuclein seed amplification assays will be performed according to the protocol developed by Cheng Ma and colleagues and implemented in the Amprion platform (The Lancet Neurology, 2024). | 3 months |
Biological signature of Parkinson's disease | Plasma proteomic profiling will be performed using proximity extension assay (PEA) technology to identify biomarker signatures associated with Parkinson's disease. In addition, plasma biomarkers related to neurodegeneration and Alzheimer's disease pathology, including phosphorylated tau (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), will be measured in participants who do not undergo lumbar puncture.
Clinical diagnosis and, when available, cerebrospinal fluid (CSF) biomarker results will be used as reference standards to identify blood-based biomarker profiles associated with Parkinson's disease.
Additional peripheral biomarker assessments will include α-synuclein seed amplification assays performed on olfactory mucosa and skin biopsy samples. Proton magnetic resonance spectroscopy (¹H-MRS) of the brain will also be performed to explore metabolic signatures associated with Parkinson's disease. | 12 months |
patients with clinical diagnosis of Parkinson's disease, atypical parkinsonisms, Alzheimer's disease, healthy volunteers, people with subjective cognitive decline.
Relevant comorbidities: chronic kidney disease (significant alteration of blood biomarkers)
Skin biopsy: local skin infection at biopsy site, severe dermatologic disease at sampling area, known bleeding disorder, significant thrombocytopenia, anticoagulation not safely manageable, allergy to local anesthetics, poor wound healing, severe peripheral vascular disease, high-risk immunosuppression, inability to consent or cooperate, extensive scarring at intended site
Magnetic resonance spectroscopy: non-MRI-compatible implanted device, ferromagnetic intracranial clip, metallic foreign body, severe claustrophobia not manageable, inability to remain still, MRI-conditional device not meeting safety conditions, pregnancy per institutional policy, severe agitation or confusion, body size exceeding scanner limits, severe motion disorder affecting acquisition
Venipuncture: refusal or inability to consent, local infection at puncture site, severe coagulopathy, marked thrombocytopenia, high bleeding risk anticoagulation, severe anemia relative to planned blood volume, difficult venous access, history of severe vasovagal syncope
Eligibility Criteria
Inclusion Criteria:
Adults able to provide informed consent
Clinical diagnosis of Parkinson's disease
Clinical diagnosis of atypical parkinsonism
Clinical diagnosis of Alzheimer's disease
Individuals with subjective cognitive decline
Healthy volunteers
Exclusion Criteria:
Acute neurological diseases
Other neurodegenerative diseases not included in the study groups (e.g., frontotemporal dementia, vascular dementia)
History of stroke with significant neurological sequelae
Chronic kidney disease with significant alteration of blood biomarkers
Procedure-specific exclusion criteria
Skin biopsy:
Local skin infection at biopsy site
Severe dermatologic disease at sampling area
Known bleeding disorder
Significant thrombocytopenia
Anticoagulation not safely manageable
Allergy to local anesthetics
Poor wound healing
Severe peripheral vascular disease
High-risk immunosuppression
Inability to consent or cooperate
Extensive scarring at intended biopsy site
Magnetic resonance spectroscopy (MRS):
Non-MRI-compatible implanted device
Ferromagnetic intracranial clip
Metallic foreign body incompatible with MRI
Severe claustrophobia not manageable with standard procedures
Inability to remain still during MRI acquisition
MRI-conditional device not meeting safety conditions
Pregnancy according to institutional MRI safety policy
Severe agitation or confusion preventing examination
Body size exceeding scanner limits
Severe motion disorder affecting acquisition
Venipuncture:
Refusal or inability to provide consent
Local infection at puncture site
Severe coagulopathy
Marked thrombocytopenia
High bleeding risk due to anticoagulation
Severe anemia relative to planned blood draw volume
Difficult venous access
History of severe vasovagal syncope during venipuncture
Lumbar puncture:
Signs of increased intracranial pressure due to mass lesion
Local infection at puncture site
Uncorrected coagulopathy
Severe thrombocytopenia
Anticoagulation not safely interruptible
Spinal cord compression
Unstable spine
Refusal or inability to cooperate with the procedure
Severe spinal deformity
Prior lumbar surgery complicating access
Severe anxiety or intolerance to the procedure
Pregnancy requiring procedural precautions
Nasal brushing:
Significant nasal polyposis
Severe septal deviation preventing access to the olfactory cleft
Active acute or chronic rhinosinusitis
Recent epistaxis or bleeding-prone nasal mucosa
Nasal lesions, ulcers, or tumors
Recent nasal surgery Nasal brushing: Significant nasal polyposis, Severe septal deviation preventing access to the olfactory cleft, Active acute or chronic rhinosinusitis, Recent epistaxis or bleeding-prone nasal mucosa, Nasal lesions, ulcers, tumors, or recent nasal surger
Azienda Ospedaliera di Perugia- Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
- IRCCS Centro Neurolesi Bonino Pulejo
Messina
Milano