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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease (PD)
• Intervention / Treatment: Other: Blood draw for the laboratory assessment

Detailed Description

The VαMPiRE study (Validation of α-synuclein Modifications in Parkinson's dIsoRder Evolution) is a multicenter, longitudinal observational study in the context of European Grant Horizon Europe (101156370-2) and is designed to validate specific α-synuclein (α-Syn) isoforms and their post-translational modifications as biomarkers for the early detection and progression monitoring of Parkinson's disease (PD). The study addresses the critical unmet need for a cost-effective, non-invasive diagnostic method by combining innovative biochemical analyses, artificial intelligence (AI)-driven data models, and comprehensive clinical assessments. This effort aligns with emerging global priorities to enhance the early diagnosis and personalized treatment of neurodegenerative diseases.

• Study Type: Observational
• Enrollment (Estimated): 1200

Contacts and Locations

• Study Contact: Name: Elda Judica, MD; Phone Number: +39 0248593242; Email: e.judica@casadicuraigea.it
• Study Contact Backup: Name: Annunziata Tramontano; Phone Number: 0039 0248593197; Email: a.tramontano@casadicuraigea.it

Study Locations

• Greece
  • Thessaloniki, Greece, 54124
    • Recruiting
    • Aristotle University of Thessaloniki
    • Contact: Savvas Petanidis; Phone Number: 0030 2310999205; Email: spetanid@auth.gr
• Italy
  • Mi
    • Milan, Mi, Italy, 20144
      • Recruiting
      • Casa di Cura Igea
      • Contact: Elda Judica, MD; Phone Number: 0039 02 48593242; Email: e.judica@casadicuraigea.it
• Poland
  • Warsaw, Poland, 02-957
    • Recruiting
    • Instytut Psychiatrii i Neurologii
    • Contact: Tomasz Stępień; Phone Number: 0048 22458 25 00; Email: tstepien@ipin.edu.pl
• Spain
  • Madrid, Spain, 28014
    • Recruiting
    • Asociacion Parkinson Madrid
    • Contact: Mayca Marin Valero; Phone Number: 0034 914 340406; Email: investigacion@parkinsonmadrid.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• 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/

Description

Inclusion Criteria:

• • 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

Exclusion Criteria:

• • For PD and non-PD subjects

  • Clinically significant and severe cognitive decline and/or intellectual disability which can lead to impairment not caused by Parkinson's disease or any other disease that could better explain the patient's symptoms; The exclusion criteria involve neurological and neurodevelopmental disorders including disorders of the brain, spinal cord, peripheral nerve, and muscle (e.g. cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury).
  • 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Parkinson (PD)	Other: Blood draw for the laboratory assessment; 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.; Other Names: Neurologic evaluation
Non-PD controls	Other: Blood draw for the laboratory assessment; 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.; Other Names: Neurologic evaluation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of AI-Generated predictive score for PD diagnosis	Development and validation of artificial intelligence (AI)-powered diagnostic algorithms utilizing multivariate biomarker data, clinical assessments, and demographic variables. The AI model generates a predictive score correlating α-Syn biomarker levels with disease onset, progression, and treatment response. The validation process evaluates the model's sensitivity, specificity, and predictive accuracy for Parkinson's Disease diagnosis.	Baseline (T0), every 3 months through periodic surveys, and 24 months post-enrollment (T1).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Assessment of Patient-Reported Quality of Life (QoL) Using PDQ-8	The Parkinson's Disease Questionnaire-8 (PDQ-8) is employed to assess changes in patient-reported quality of life (QoL) over the study period. It evaluates mobility, daily activities, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Scores are analyzed to monitor disease burden and its correlation with α-Syn biomarker levels.	Baseline (T0) and 24 months post-enrollment (T1).

Collaborators and Investigators

• Sponsor: Casa di Cura IGEA
• Collaborators: Aristotle University Of Thessaloniki; Institute of Psychiatry and Neurology, Warsaw; Asociación Parkinson Madrid; LINKCARE HEALTH SERVICES SL; ALMAWAVE SPA; European Brain Research Foundation
• Investigators: Principal Investigator: Elda Judica, MD, Casa di Cura Igea; Study Chair: Marco Feligioni, PHD, EBRI-European Brain Research Insitute

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: α-Synuclein
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Parkinson Disease 4, Autosomal Dominant Lewy Body; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 101156370

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) related to primary and secondary outcomes, demographic and baseline characteristics will be made available to qualified researchers upon reasonable request, following publication of study results. Data will be shared through appropriate data repositories and in compliance with applicable ethical and legal regulations. Via submission of a data access request to the study sponsor. Data will be shared through a secure institutional repository (e.g., Zenodo, ORE, EOSC).Key Exploitable Results will be disseminated through the Horizon Results Platform.
• IPD Sharing Time Frame: Starting 6 months after publication of the main study results. For a period of 5 years following publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No