Exploring the Olfactory Mucosa, Blood and Urine for the Identification of Early Biomarkers of Parkinson's Disease, Atypical Parkinsonisms and Neurocognitive Disorders Due to Lewy Body Disease

NCT06846658 | Recruiting

• 1 other identifier: GR 2021 12372019
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 3

Brief Summary

Clinical diagnosis of Parkinson's disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) is challenging, especially in the early stages. Each disease is associated with distinct conformers of misfolded alpha-synuclein (maS) which form typical protein aggregates in the brain and represent key disease biomarkers. Thus, detection and characterization of intracerebral maS aggregates allow a definite diagnosis. The recent development of ultrasensitive assays enabled the detection of maS and other potential new biomarkers in peripheral tissues, although with several limitations. Here, the investigators propose to combine the expertise of leading and young researchers in the field of neurology, structural and molecular biology, biophysics and machine learning to perform ultrasensitive and multi-omics analyses of olfactory mucosa (OM), blood and urine of PD, MSA and DLB patients for detecting and characterizing key peripheral biomarkers allowing accurate disease recognition.

Conditions

Parkinson Disease; MSA - Multiple System Atrophy; Lewy Body Dementia (LBD); Neurodegenerative Disease; Healthy Subjects (HS)

Keywords

Parkinson's disease (PD); multiple system atrophy (MSA); dementia with Lewy bodies (DLB); misfolded alpha-synuclein; new biomarkers; peripheral tissues; Real-Time Quaking-Induced Conversion (RT-QuIC); single-molecule array (Simoa); circulating neurofilament light chain (NfL); Nanoparticle Tracking Analysis (NTA); blood-derived extracellular vesicles (EVs); multi-omics analyses; transmission electron microscopy (TEM) and protein-NMR; protein misfolding; early diagnosis

Outcome Measures

Primary Outcomes (1)

• Identify a predictive model for the diagnosis of PD, MSA and DLB

  To identify a predictive model for the diagnosis of PD, MSA and DLB based on the integration of: * Demographic and clinical: sex, age, comorbidities, disease duration and severity, current medications, cognitive status, the presence of bradykinesia, rigidity, tremors, orthostatic hypotension, autonomic failure, parkinsonism, visual hallucinations, cerebellar syndrome, dementia, rapid eye movement sleep behavior disorder; * Instrumental data: MRI, dopamine-transporter single-photon emission computerized tomography (DAT-SPECT), iodine-131-meta-iodobenzylguanidine (MIBG), fluorodeoxyglucose positron emission tomography (FDG-PET); * Results obtained from the biochemical, structural and RT-QuIC analyses of olfactory mucosa, blood and urine samples (gathered in detailed in the secondary outcomes measures paragraph).

  3 years

Secondary Outcomes (6)

• Analysis of olfactory functions.

  12 months

• Evaluation of RT-QuIC accuracy in detecting maS in OM, blood- and urine-derived EVs

  21 months

• Ultrasensitive detection and measurement of known or potential new biomarkers in OM, blood and urine of enrolled patients by Simoa SR-X.

  18 months

• Ultrasensitive detection and measurement of known or potential new biomarkers in OM, blood and urine of enrolled patients by ELISA.

  18 months

• NTA Nano-Sight NS300 analysis of concentration and size of EVs circulating in blood and urine.

  24 months

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

PD (n=20), MSA (n=20), DLB (n=20), OND (n=10, including acquired and hereditary ataxic syndrome with known etiology, progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease) and HS (n=10).

You may qualify if:

• PD (Postuma et al., 2015), MSA (Palma et al., 2018), DLB (McKeith et al., 2017), OND including acquired and hereditary ataxic syndrome with known etiology, progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease.

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (3)

Consorzio Interuniversitario Risonanze Magnetiche Metallo Proteine (CIRMMP)

Sesto Fiorentino, FI, 50019, Italy

RECRUITING

IRCCS Centro San Giovanni di Dio

Brescia, 25125, Italy

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Shy-Drager Syndrome; Lewy Body Disease; Neurodegenerative Diseases; Multiple System Atrophy; Familial cylindromatosis; Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Primary Dysautonomias; Autonomic Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases; Dementia; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Fabio Moda, PHD

  Fondazione IRCCS Istituto Neurologico Carlo Besta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2025
• First Posted: February 26, 2025
• Study Start: October 3, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF

Locations

IT (3)