An interventional study of brain imaging and blood draw in Parkinson's Disease (PD), GBA1 Parkinson Disease and REM Sleep Behavior Disorder (iRBD), sponsored by University of Pavia. Not yet recruiting at 2 sites in Italy. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-05-01.
Sponsored by University of Pavia · Not applicable, Interventional, and Basic science
The project aims to investigate how abnormal accumulation of alpha synuclein and its interaction with tau influence brain function across the Parkinson's disease (PD) spectrum, with particular focus on individuals carrying GBA1 mutations. This interventional, monocentric, cross sectional study includes patients with PD, individuals with idiopathic REM sleep behavior disorder, and participants without PD.
All enrolled subjects will undergo clinical and neuropsychological assessments, blood based biomarker analyses related to neurodegeneration, synaptic and mitochondrial function, and multimodal brain MRI to evaluate brain structure, white matter integrity, and functional connectivity.
The study aims to:
In parallel, preclinical studies in GBA PD mouse models and wild type mice will be used to investigate how changes in PD-related pathology (alpha-synuclein and tau) relates to behavior, brain imaging alterations and mitochondrial, axonal and synaptic damage. Animal model will also aid the validation of a new PET tracer that targets alpha synuclein (i.e., [¹⁸F]Syntacasyn).
Together, human and preclinical studies are designed to provide a translational framework integrating molecular changes with brain network alterations and clinical heterogeneity in PD.
Parkinson's disease (PD) is characterized by pathological aggregation and propagation of alpha synuclein, leading to synaptic and mitochondrial dysfunction. Heterozygous mutations in the GBA1 gene represent the strongest genetic risk factor for PD and are associated with earlier onset, faster progression, and increased burden of misfolded alpha synuclein. Experimental evidence suggests that alpha synuclein toxicity may be amplified by its interaction with tau, promoting synergistic neurodegenerative mechanisms; however, in vivo human data on these processes remain limited.
This study aims to define, through a personalized and multimodal approach, how alpha synuclein accumulation and its interaction with tau influence synaptic and mitochondrial dysfunction and brain connectivity across the PD spectrum, from periclinal stages to established disease, with particular focus on the impact of GBA1 mutations. The study includes patients with PD, individuals with idiopathic REM sleep behavior disorder (iRBD), and subjects without PD, both carriers and non carriers of GBA1 mutations.
All participants will undergo comprehensive clinical and neuropsychological assessments to characterize motor, non motor, and cognitive manifestations across disease stages. Blood samples will be collected to define a fluid biomarker profile, including alpha synuclein, tau, markers of synaptic integrity, mitochondrial function, and neurodegeneration. In addition, all participants will undergo multimodal brain MRI, including structural, diffusion weighted, and resting state functional sequences, to evaluate brain structure, white matter integrity, and functional connectivity.
In a subset of participants, a skin biopsy will be performed to generate patient specific induced pluripotent stem cell (hiPSC) derived dopaminergic neurons. These cellular models will be used to investigate neuronal and synaptic function in relation to individual biomarker profiles and genetic background. In parallel, preclinical studies will be conducted in GBA-PD mouse models and wild type mice injected with saline, alpha synuclein or combined alpha synuclein/tau fibrils. Mice will undergo behavioral, in vivo MRI and PET imaging and post mortem assessment of synaptic, axonal and mitochondrial pathology. In addition, a novel alpha synuclein PET tracer, [¹⁸F]Syntacasyn, will undergo preclinical validation.
Multimodal human and animal data will be integrated using advanced statistical and computational approaches to identify vulnerable network hubs and generate subject specific "virtual brain" models of alpha synuclein pathology propagation.
The study is designed to provide a translational framework linking molecular pathology, brain network dysfunction and clinical heterogeneity in PD, supporting biomarker development and precision medicine strategies across the prodromal and clinical spectrum, with particular focus on genetically defined populations such as GBA1 mutation carriers.
4,573 studies on the registry are indexed under Parkinson Disease; 1,086 are open to participants now.
This study's planned enrollment of 160 is above the median of 40 across 3,353 interventional studies indexed under Parkinson Disease.
Browse Parkinson Disease studies →University of Pavia is the lead sponsor of 144 studies on the registry; 39 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion criteria for Parkinson's disease cohorts (GBA-PD and nonGBA-PD):
Exclusion criteria for Parkinson's disease cohorts:
Inclusion criteria for unaffected subjects (GBA-nonPD and nonGBA-nonPD):
Exclusion criteria for unaffected subjects (GBA-nonPD and nonGBA-nonPD):
Inclusion criteria for subjects with idiopathic REM Sleep Behavior Disorder (GBA-iRBD and nonGBA-iRBD):
Exclusion criteria for subjects with idiopathic REM Sleep Behavior Disorder (GBA-iRBD and nonGBA-iRBD):
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Diagnostic Test: brain imaging Procedure/Surgery: blood draw, skin biopsy
Diagnostic Test: brain imaging · Procedure: blood draw · Procedure: Skin biopsy
Diagnostic Test: brain imaging Procedure/Surgery: blood draw, skin biopsy
Diagnostic Test: brain imaging · Procedure: blood draw · Procedure: Skin biopsy
Diagnostic Test: brain imaging Procedure/Surgery: blood draw, skin biopsy
Diagnostic Test: brain imaging · Procedure: blood draw · Procedure: Skin biopsy
Diagnostic Test: brain imaging Procedure/Surgery: blood draw, skin biopsy
Diagnostic Test: brain imaging · Procedure: blood draw · Procedure: Skin biopsy
Diagnostic Test: brain imaging Procedure/Surgery: blood draw
Diagnostic Test: brain imaging · Procedure: blood draw
Diagnostic Test: brain imaging Procedure/Surgery: blood draw
Diagnostic Test: brain imaging · Procedure: blood draw
Participants will undergo a single brain MRI acquisition, including structural, diffusion-weighted, and resting-state functional MRI.
Collection of a venous blood sample for biochemical analyses
A small punch skin biopsy (about 3-4 mm) will be performed under local anesthesia on a small sample of enrolled participants (n=10)
Concentration of alpha-synuclein levels in plasma
Quantification of levels of Total alpha-synuclein and 129P-alpha-synuclein (pg/ml) in neuronal-derived extracellular vesicles using ultrasensitive immunoassays (NULISA).
Time frame: Baseline visit
Concentration of tau levels in plasma
Quantification of total-tau and p-tau18 (pg/ml) in neuronal-derived extracellular vesicles using ultrasensitive immunoassays (NULISA).
Time frame: Baseline visit
Investigation of glucocerebrosidase activity in Peripheral Blood Mononuclear Cells
Glucocereborsidase activity will be estimated in Peripheral Blood Mononuclear Cells usign a flourimetry assay
Time frame: Baseline visit
Assessment of mitochondrial damage in plasma
Quantification of circulating cell-free mitochondrial DNA (cf-mtDNA) in plasma, including total concentration and deletion fraction.
Time frame: Baseline visit
Plasma synaptic protein concentration
Quantification of SNAP25, STX1A, and VAMP2 in neuronal-derived extracellular vesiclesusing ultrasensitive immunoassay (NULISA)
Time frame: Baseline visit
Brain network connectivity in Parkinson's disease
We will exctract structural and functional connectivity information form MRI, resting-state functional MRI and diffusion weighted MRI. Connectivity metrics will include global and nodal efficiency, participation coefficient and indexes of withe matter tract integrity.
Time frame: Baseline visit
In vitro neuronal responses in hiPSC-derived dopaminergic neurons
In vitro neuronal responses will be assessed in dopaminergic neurons derived from human induced pluripotent stem cells (hiPSC), following exposure to alpha-synuclein and alpha-synuclein+tau.
Time frame: Baseline visit
Estimation of synaptic damage in Neuronal extracellular vesicle
Neurogranin concentration (pg/ml) will be quantified in neuronal-derived extracellular vesicles
Time frame: Baseline visit
Concentration of neurofilament light chain
Neurofilament light chain concentration (pg/ml) will be quantified in plasma using Ella™.
Time frame: Baseline visit
Comprehensive clinical and neuropsychological assessement
Time frame: Baseline visit
Plan to share: No
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