Exercise and Plasticity in Parkinson Disease

Exercise and Plasticity in PD: Functional and Structural Evidence in the Cortex and the Spinal Cord

We will study the effects of intensive rehabilitation in PD on plasticity with a multimodal approach. We will define first, whether exercise in PD restores the potentiation of the motor cortex to normal levels with both 5 Hz-rTMS PAS and beta modulation and whether such improvements are accompanied by structural changes studied with diffusion MRI tractography and network analysis (Aim 1). With the study of muscle synergies and spatiotemporal organization of the spinal motoneuronal output during gait and reaching movements we will define the presence of functional changes in spinal cord mechanisms and connectivity and whether such changes are global or involve selective districts (Aim 2). Finally, we will study post-exercise changes in sleep pattern, as sleep is impaired in PD and plays a crucial role in the definition of plasticity-related phenomena (Aim 3). This project will generate breakthrough data on the mechanisms of exercise, novel biomarkers to monitor efficacy of treatments and thus, possibly leading to better restorative, disease-modifying and symptomatic therapies for PD.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: experimental group MIRT; Device: EEG task rTMS, fMRI

Detailed Description

We will study the effects of intensive rehabilitation in PD on plasticity with a multimodal approach. We will define first, whether exercise in PD restores the potentiation of the motor cortex to normal levels with both 5 Hz-rTMS PAS and beta modulation and whether such improvements are accompanied by structural changes studied with diffusion MRI tractography and network analysis (Aim 1). With the study of muscle synergies and spatiotemporal organization of the spinal motoneuronal output during gait and reaching movements we will define the presence of functional changes in spinal cord mechanisms and connectivity and whether such changes are global or involve selective districts (Aim 2). Finally, we will study post-exercise changes in sleep pattern, as sleep is impaired in PD and plays a crucial role in the definition of plasticity-related phenomena (Aim 3)

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: silvia marino, MD; Phone Number: 09060128110; Email: silvia.marino@irccsme.it

Study Locations

• Italy
  • Messina, Italy, 98124
    • Recruiting
    • IRCCS Centro Neurolesi "Bonino-Pulejo"
    • Contact: Rossella Ciurleo; Email: rossella.ciurleo@irccsme.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Idiophatic Parkinson Disease

• H&Y stage I-II stable medication

Exclusion Criteria:

• Severe comorbid medical illness (diabetes, heart disease, hypertension); history of known causative factors (encephalitis or neuroleptic treatment); other neurologic disability; chronic treatment for sleep complaints; history of seizure, including febrile seizures, family history of epilepsy; pacemakers, neurostimulators, tattoos, metal foreign bodies in the head area; recurrent visual hallucinations; fluctuating cognition, attention or alertness; depression (HAMD> 12) or dementia (MMSE <24).

Controls will be age- and education- matched subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group MIRT; Task 1a: Assessing the effect of MIRT on cortical plasticity tested with rPAS Task 1b: Assessing the effect of MIRT on structural cortical plasticity and brain connectivity tested with MRI Task 1c: Assessing the effect of MIRT on movement-related beta modulation Task 1d: Assessing the effects of MIRT on motor skills formation with reaching tasks Task 1e: Assessing the effects of MIRT on EEG correlates of motor skills formation Task 2a: Assessing the effect of MIRT on muscle synergies during gait Task 2b: Assessing the effect of MIRT on muscle synergies during reaching movements Task 3a: Assessing the effect of MIRT on sleep microstructure	Device: experimental group MIRT; Task 1a: Assessing the effect of MIRT on cortical plasticity tested with rPAS Task 1b: Assessing the effect of MIRT on structural cortical plasticity and brain connectivity tested with MRI Task 1c: Assessing the effect of MIRT on movement-related beta modulation Task 1d: Assessing the effects of MIRT on motor skills formation with reaching tasks Task 1e: Assessing the effects of MIRT on EEG correlates of motor skills formation Task 2a: Assessing the effect of MIRT on muscle synergies during gait Task 2b: Assessing the effect of MIRT on muscle synergies during reaching movements Task 3a: Assessing the effect of MIRT on sleep microstructure; Device: EEG task rTMS, fMRI; EEG task rTMS, fMRI
Active Comparator: control group; EEG con task, Gait Analysis, fMRI, rTMS,	Device: EEG task rTMS, fMRI; EEG task rTMS, fMRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
functional magnetic resonance	assessment of the functional and structural plasticity changes after MIRT	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EMG	muscle synergies and spatiotemporal organization of the spinal motoneuronal output during gait and reaching movements we will define the presence of functional changes in spinal cord mechanisms and connectivity and whether such changes are global or involve selective districts	1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PS EEG	we will study post-exercise changes in sleep pattern, as sleep is impaired in PD and plays a crucial role in the definition of plasticity-related phenomena	1 month

Collaborators and Investigators

• Sponsor: IRCCS Centro Neurolesi "Bonino-Pulejo"
• Investigators: Principal Investigator: felice ghilardi, MD, City College of New York, New York, NY

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2021
• Primary Completion (Anticipated): February 10, 2024
• Study Completion (Anticipated): February 10, 2024

Study Registration Dates

• First Submitted: March 15, 2023
• First Submitted That Met QC Criteria: March 15, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: PD180091

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Principal Investigator

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No