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

NCT05807581 | Unknown

• 1 other identifier: 5478
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (4)

• 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

• 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

• 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

Study Arms (5)

Biomarkers

NO INTERVENTION

physical activity

ACTIVE COMPARATOR

Other: physical activity

sedentary

NO INTERVENTION

iTBS active

ACTIVE COMPARATOR

Other: iTBS

iTBS sham

SHAM COMPARATOR

Other: iTBS

Interventions

physical activity OTHER

treadmill running 3 times weekly

physical activity

iTBS OTHER

repetitive TMS stimulation 5 days weekly for two weeks

iTBS active; iTBS sham

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• clinically established diagnosis of PD according to the Movement Disorders Society (MDS) diagnostic criteria
• Hoehn \& Yahr (H\&Y) stage between 1 and 3

You may not qualify if:

• Pregnancy
• Oncological or autoimmune comorbidities

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• IRCCS National Neurological Institute "C. Mondino" Foundation: collaborator
• Istituto Neurologico Mediterraneo Neuromed S. R. L: collaborator
• Azienda Ospedaliera Universitaria Policlinico "G. Martino": collaborator

Study Sites (1)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

Exercise

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

FLAVIA TORLIZZI

CONTACT

0630155633; flavia.torlizzi@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: April 11, 2023
• Study Start: June 9, 2023
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: March 13, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)