Clinical trial NCT06941012: Validation of α-synuclein Modifications in Parkinson's dIsoRder Evolution
Official title: Validation of α-synuclein Modifications in Parkinson's dIsoRder Evolution (VaMPiRE)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Parkinson Disease (PD)
Keywords: α-Synuclein
Lead sponsor: Casa di Cura IGEA
Sponsor class: OTHER
Collaborators: name: Asociación Parkinson Madrid
name: Aristotle University Of Thessaloniki
name: Institute of Psychiatry and Neurology, Warsaw
name: LINKCARE HEALTH SERVICES SL
name: ALMAWAVE SPA
name: European Brain Research Foundation
First posted: 2025-04-23
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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/

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Quantification of α-Synuclein Isoforms (-140, -126, -112, -98) and Their SUMOylated Forms in NDEVs from Blood Samples
timeFrame: Baseline (T0) and 24 months post-enrollment (T1).
Secondary outcomes:
measure: Validation of AI-Generated predictive score for PD diagnosis
timeFrame: Baseline (T0), every 3 months through periodic surveys, and 24 months post-enrollment (T1).
Other outcomes:
measure: Longitudinal Assessment of Patient-Reported Quality of Life (QoL) Using PDQ-8
timeFrame: Baseline (T0) and 24 months post-enrollment (T1).
Locations:
city: Thessaloniki
country: Greece
facility: Aristotle University of Thessaloniki
city: Milan
country: Italy
facility: Casa di Cura Igea
state: Mi
city: Warszawa
country: Poland
facility: Instytut Psychiatrii I Neurologii
city: Madrid
country: Spain
facility: Asociacion Parkinson Madrid
Study officials:
affiliation: EBRI-European Brain Research Insitute
name: Marco Feligioni, PHD
role: STUDY_CHAIR
affiliation: Casa di Cura IGEA
name: Elda Judica, MD
role: PRINCIPAL_INVESTIGATOR
References: