Clinical, Molecular and Electrophysiological Profiling of Parkinson's Disease: the Role of Non-pharmacological Therapies
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Parkinson Disease
- Sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- MOLECULAR PROFILING OF PD PATIENTS (n=400)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
In Parkinson's disease (PD), direct evidence linking inflammation to the harmful activities of alpha-synuclein (a-syn) aggregates, the disease onset, and its progression is still lacking. This translational project aims to reveal the causal relationship between a-syn and inflammation. The investigators will also investigate the mechanisms underlying the beneficial effects of two non-pharmacological approaches, motor exercise and neuromodulation, with particular focus on neuroinflammation and brain-derived neurotrophic factor (BDNF) production. the investigators will investigate the molecular pathways and synaptic alterations underlying disease progression. This will be paralleled by a clinical study, in which clinical assessment will be associated with cerebrospinal fluid (CSF) and blood neurodegeneration and inflammatory biomarkers measures. Then, the investigators will test the hypothesis that intensive exercise and neuromodulation may reduce neuroinflammation and a-syn spreading via the activation of BDNF-related pathways.
Investigators
Eligibility Criteria
Inclusion Criteria
- •clinically established diagnosis of PD according to the Movement Disorders Society (MDS) diagnostic criteria
- •Hoehn \& Yahr (H\&Y) stage between 1 and 3
Exclusion Criteria
- •Pregnancy
- •Oncological or autoimmune comorbidities
Outcomes
Primary Outcomes
MOLECULAR PROFILING OF PD PATIENTS (n=400)
Time Frame: at enrolling
Biomarkers related to axonal damage (total tau (t-Tau), neurofilament light chain, (NfL), and phosphorylated neurofilament heavy chain, (p-NfH), synaptic dysfunction (a-synuclein (a-syn) and neurogranin, (Ng)), neuroinflammation (soluble triggering receptor expressed on myeloid cells 2, sTREM2, and chitinase-3- like protein 1, YKL-40) will be analysed in cerebrospinal fluid (CSF) and blood samples and extracellular vesicles (EVs) (UO1, UO2) (for all the biomarkers, ng/ml).
CLINICAL PROFILING OF PD PATIENTS (n=400)
Time Frame: at enrolling
patients will be evaluated by means of validated clinical scales Non-Motor Symptoms scale (min 0- 360 max , better clinical conditions has lower scores)
ELECTROPHYSIOLOGICAL PROFILING OF PD PATIENTS (n=400)
Time Frame: at enrolling
Motor evoked potentials (MEPs) from the First Digital Interosseus muscle of the most affected hand of each patient, a brief pattern of iTBS will be applied to promote enhancement of cortical excitability. MEPs size will be then assessed again using single-pulse TMS.
Secondary Outcomes
- NMSS CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240) CLINICAL PROFILING OF PD PATIENTS (n=400)(at the end of the non-pharmacological intervention (2 weeks for TMS branches, 3 months for physical activity branches) and 3 and 6 months after)
- UPDRS CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240) CLINICAL PROFILING OF PD PATIENTS (n=400)(at the end of the non-pharmacological intervention (2 weeks for TMS branches, 3 months for physical activity branches) and 3 and 6 months after)
- MOLECULAR CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240)(at the end of the non-pharmacological intervention (2 weeks for TMS branches, 3 months for physical activity branches) and 3 and 6 months after)
- ELECTROPHYSIOLOGICAL CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240)(at the end of the non-pharmacological intervention (2 weeks for TMS branches, 3 months for physical activity branches) and 3 and 6 months after)