Validation of α-synuclein Modifications in Parkinson's dIsoRder Evolution

NCT06941012 | Recruiting DMC

• 1 other identifier: 101156370
• Study Type: observational
• Target: 1,200
• Locations: 4 countries
• Sites: 4

Brief Summary

Parkinson's disease (PD) presents a complex challenge due to its progressive neurodegenerative nature, affecting various bodily systems. Despite decades of research, understanding its onset and progression remains unclear, complicating early diagnosis and treatment. Recent advances in PD pathophysiology suggest promising treatments to slow disease progression, yet reversing cellular degeneration remains elusive. With novel therapies emerging, the need for early detection tools is urgent. However, validated biomarkers for PD diagnosis are lacking, relying on subjective scales like Hoehn and Yahr or costly medical imaging techniques. The accumulation of misfolded α-Synuclein (α-Syn) proteins in PD pathology has sparked interest, but defining diagnostic roles requires further investigation. Recent findings of α-Syn in neuronal-derived extracellular vesicles (NDEVs) from PD patients suggest a potential for novel diagnostic methods. Our proposed project, VαMPiRE, aims to conduct a longitudinal study involving 600 PD and 600 non-PD participants using a cluster-adjusted case-control methodology, to explore α-Syn isoforms and related biomarkers in NDEVs for early PD detection. We plan to develop and validate an innovative in-vitro diagnostic (IVD) test capable of detecting PD's earliest stages and estimating disease prognosis and progression. Utilizing AI models to generate data analysis algorithms and collaboration with leading analytical laboratories and IVD manufacturers, we aim to ensure the reliability and feasibility of the developed prototype. Through consortium efforts, we envision licensing the generated intellectual property to drive the commercialization of our results. Two round of blood sample extractions will be performed within a 24-month gap to PD participants and a single baseline for non-PD controls. All participants will be regularly followed up during this 24-month period to monitor disease evolution and treatment, and non-PD controls developing the disease will be part of a third cohort (expected to be around 24 subjects according to 4% incidence) that will confirm the sensitivity of the test in asymptomatic subjects. The unique aspect of the project is that we anticipate being able to detect theses 4% of non-PD participants that will go on to develop the disease, therefore demonstrating the value of these biomarkers to identify PD early. The prototype will be validated for its discriminative capacity, using the first baseline set of PD and non-PD samples, and for its ability to detect the PD-progression comparing baseline and 24-months data plus blood samples. Improved early screening could allow for 270,000 new cases of PD to be detected earlier, improve the disease management of 9.4 M people currently diagnosed of PD and avoid losing a total of 5.8 million disability adjusted life years (DALYs) by 2028 leading also the development of better treatments.

Conditions

Parkinson Disease (PD)

Keywords

α-Synuclein

Outcome Measures

Primary Outcomes (1)

• Quantification of α-Synuclein Isoforms (-140, -126, -112, -98) and Their SUMOylated Forms in NDEVs from Blood Samples

  The primary outcome measure involves the quantification of α-synuclein (α-Syn) isoforms (-140, -126, -112, -98) and their SUMOylated forms in neuronal-derived extracellular vesicles (NDEVs) isolated from blood samples. Advanced biochemical techniques, including lateral flow immunoassay coupled with digital readers, are employed for precise quantification. AI-driven data analysis evaluates correlations between biomarker levels and Parkinson's Disease (PD) progression. Clinical Implications: This outcome aims to validate α-Syn biomarkers for early PD diagnosis, offering a non-invasive, cost-effective alternative to current methods like DaT imaging. Reliable identification of α-Syn isoforms could improve early intervention strategies, slow disease progression, and support personalized treatment plans. Additionally, it could provide insights into disease mechanisms, enhancing future therapeutic developments and enabling scalable, accessible diagnostic solutions globally.

  Baseline (T0) and 24 months post-enrollment (T1).

Secondary Outcomes (1)

• Validation of AI-Generated predictive score for PD diagnosis

  Baseline (T0), every 3 months through periodic surveys, and 24 months post-enrollment (T1).

Other Outcomes (1)

• Longitudinal Assessment of Patient-Reported Quality of Life (QoL) Using PDQ-8

  Baseline (T0) and 24 months post-enrollment (T1).

Study Arms (2)

Parkinson (PD)

Other: Blood draw for the laboratory assessment

Non-PD controls

Other: Blood draw for the laboratory assessment

Interventions

Blood draw for the laboratory assessment OTHER

Participants' clinical histories will be reviewed at T0 (baseline) and T1 (24 months). They will also undergo a clinical assessment at T0 and T1. The assessments will be tailored based on whether the participant belongs to the PD or non-PD group, as outlined below: • MDS-UPDRS + H\&Y: Used to evaluate the neurological domain, applied to the PD group. • BERG: Used to assess balance and performance, applied to both PD and non-PD groups. • CIRS-G: Used to evaluate comorbidities, applied to both PD and non-PD groups. • PD-CRS: Used to assess cognitive function, applied to the PD group. • MMSE (temporal and spatial orientation only): Used to assess cognitive function, applied to both PD and non-PD groups. • PDQ-8: Used to evaluate quality of life, applied to the PD group. • PD-CFRS: Used for functional assessment, applied to the PD group. • GDS: Used to assess depression, applied to both PD and non-PD groups. Blood samples will be collected at T0 and T1, with 20 mL drawn per participant.

Also known as: Neurologic evaluation

Non-PD controls; Parkinson (PD)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Recruitment will be conducted across five clinical sites, with each site contributing based on its recruitment capacity and resources. PD patients and non-PD controls will be recruited among similar characteristics. A matched case-control approach will be implemented to meet the study's objectives. Matching will be used to control for potential confounding factors. By pairing or grouping participants with PD (cases) and those without PD (non-PD controls) based on shared characteristics-such as age, gender, geographic location, and relevant comorbidities (e.g., type 2 diabetes, hypertension, anemia, gastrointestinal dysfunction, etc.)-we aim to reduce bias and enhance statistical efficiency in adjusted analysis. As it will be difficult to exactly match all cases with equivalent controls, we will use the stratification to cluster PD and non-PD participants so comparative analysis can be performed between PD and non-PD equivalent clusters. Each time a participant is recruited into PD, he/

You may qualify if:

• For PD subjects
• PD diagnosis according to MDS-UPDRS criteria and Hoehn and Yahr scale between I-IV (MED ON) for PD subjects
• Willing to participate. Participation is always voluntary.
• Willing and able to provide written informed consent to participate in the study or having a legal representative responsible for signing; the participant (or the legal representative) must understand the purpose, methods, and all information regarding the study.
• For non-PD subjects
• Normal neurological examination findings.
• Medical record (recent and remote medical history) available and reviewable by clinicians during the entire study period.
• Willing and able to provide written informed consent to participate in the study

You may not qualify if:

• For PD and non-PD subjects
• Fever (Temperature 38.0 °C (tympanic)).
• Acute infection (such as Flu, COVID-19) which could debilitate the patient and affect the data.
• Individuals with concurrent infections requiring systemic antimicrobial and/or antiviral therapy at the pre-dose examinations (e.g. HepC, HIV, TB).
• Life-threatening co-existing disease with life expectancy, which could lead to premature dropout.
• Any other neurological or systemic conditions that could confound results.

Sponsors & Collaborators

• Institute of Psychiatry and Neurology, Warsaw: collaborator
• ALMAWAVE SPA: collaborator
• European Brain Research Foundation: collaborator
• Casa di Cura IGEA: lead
• Asociación Parkinson Madrid: collaborator
• Aristotle University Of Thessaloniki: collaborator
• LINKCARE HEALTH SERVICES SL: collaborator

Study Sites (4)

Aristotle University of Thessaloniki

Thessaloniki, 54124, Greece

RECRUITING

Casa di Cura Igea

Milan, Mi, 20144, Italy

RECRUITING

Instytut Psychiatrii I Neurologii

Warsaw, 02-957, Poland

RECRUITING

Asociacion Parkinson Madrid

Madrid, 28014, Spain

RECRUITING

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Parkinson Disease; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Marco Feligioni, PHD

  EBRI-European Brain Research Insitute

  STUDY CHAIR

• Elda Judica, MD

  Casa di Cura IGEA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elda Judica, MD

CONTACT

+39 0248593242; e.judica@casadicuraigea.it

Annunziata Tramontano

CONTACT

0039 0248593197; a.tramontano@casadicuraigea.it

Study Design

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

Study Record Dates

• First Submitted: April 16, 2025
• First Posted: April 23, 2025
• Study Start: May 12, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: March 2, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting 6 months after publication of the main study results. For a period of 5 years following publication.

Locations

GR (1); PL (1); ES (1); IT (1)