Clinical, Molecular and Electrophysiological Profiling of Parkinson's Disease: the Role of Non-pharmacological Therapies

Parkinson Disease Clinical Trial

Official title:

Clinical, Molecular and Electrophysiological Profiling of Parkinson's Disease: the Role of Non-pharmacological Therapies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05807581
• Other study ID #: 5478
• Status: Recruiting
• Phase: N/A
• Start date: June 9, 2023
• Est. completion date: May 30, 2025

Study information

• Verified date: March 2023
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: FLAVIA TORLIZZI
• Phone: 0630155633
• Email: flavia.torlizzi[@]policlinicogemelli.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: May 30, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Other:
• physical activity
treadmill running 3 times weekly
• iTBS
repetitive TMS stimulation 5 days weekly for two weeks

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma

Sponsors (4)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Azienda Ospedaliera Universitaria Policlinico "G. Martino", IRCCS National Neurological Institute "C. Mondino" Foundation, Istituto Neurologico Mediterraneo Neuromed S. R. L

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CLINICAL PROFILING OF PD PATIENTS (n=400)	patients will be evaluated by means of validated clinical scales Movement disorders society-unified Parkinson's Disease Rating Scale (min 0- max 260, better clinical conditions has lower scores)	at enrolling
Primary	CLINICAL PROFILING OF PD PATIENTS (n=400)	patients will be evaluated by means of validated clinical scales Non-Motor Symptoms scale (min 0- 360 max , better clinical conditions has lower scores)	at enrolling
Primary	MOLECULAR PROFILING OF PD PATIENTS (n=400)	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).	at enrolling
Primary	ELECTROPHYSIOLOGICAL PROFILING OF PD PATIENTS (n=400)	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.	at enrolling
Secondary	UPDRS CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240) CLINICAL PROFILING OF PD PATIENTS (n=400)	patients will be evaluated by means of validated clinical scales, Movement disorders society- Unified Parkinson's disease rating scale, (min 0- 260 max , better clinical conditions has lower scores)	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
Secondary	NMSS CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240) CLINICAL PROFILING OF PD PATIENTS (n=400)	patients will be evaluated by means of validated clinical scales Non-Motor Symptoms Scale (min 0- 360 max , better clinical conditions has lower scores)	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
Secondary	MOLECULAR CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240)	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).	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
Secondary	ELECTROPHYSIOLOGICAL CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240)	Motor evoked potentials (MEPs) from the FDI 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.	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