Endurance Exercise & Virtual Reality for Optimizing Cortical Excitability and Neuroplasticity in PD

Study Overview
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Brief Summary
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This study aims to determine the effects of aerobic exercise as a primer to add-on virtual reality (VR)-based rehabilitation on balance, postural control and neuroplasticity (ability of brain to adapt in structure and function) in individuals with Parkinson's disease (PD). This study will utilize two groups - one group will receive the exercise and VR, while the other group will receive stretching exercise and VR over eight weeks. The study team will administer outcomes at baseline, post-intervention (8 weeks) and follow-up (6 weeks after post-assessment).

Detailed Description
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This study will enroll individuals diagnosed with Parkinson's disease who will be randomly assigned to 2 groups: 1) high intensity endurance exercise and virtual reality (experimental) or 2) stretching and virtual reality (control) for eight weeks (three sessions, thrice weekly). Outcomes will include balance and gait measures, blood-based biomarkers, neuroplasticity measures (assessed by transcranial magnetic stimulation), spinal reflex excitability (measured by H reflex) and quality of life.

Official Title
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High Intensity Endurance Exercise as a Primer to Virtual Reality for Optimizing Cortical Excitability and Neuroplasticity in Parkinson's Disease (PD)

Conditions
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Parkinson Disease

Intervention / Treatment
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* Behavioral: High intensity endurance exercise
* Behavioral: Stretching exercise
* Behavioral: Virtual reality (VR)-based gaming


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic PD (ages 18 -85) in Hoehn and Yahr stages 2 - 3. Subjects need to demonstrate a score of equal to or greater than 23 on the Mini Mental State Examination. Subjects who have a score of ≤21.5 on the Mini Balance Evaluations Systems Test (miniBESTest). Exclusion Criteria: Subjects with a history of other neurological diseases (i.e., stroke, multiple sclerosis). Subjects with a history of severe cardiopulmonary disease, uncontrolled hypertension, orthostatic hypotension, uncontrolled diabetes, severe osteoporosis, severe arthritis affecting their lower extremity joints. Subjects with a history of PD-specific surgical procedures such as deep brain stimulation etc. Subjects with a history of head injury. Subjects with a history of seizures or epilepsy. Subjects who are currently pregnant. Individuals who use of medications that could alter corticomotor excitability or increase risk of seizure. Individuals with skull abnormalities, fractures or unexplained, recurring headaches.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will utilize a randomized controlled design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High intensity endurance exercise and virtual reality (experimental)<br>The exercise group will perform high intensity interval exercise and VR-based games 3 times a week for 8 weeks. | Behavioral: High intensity endurance exercise<br>* High intensity interval exercise on a recumbent stepper for 30 minutes, 3 days per week.<br>Behavioral: Virtual reality (VR)-based gaming<br>* VR games will involve games that challenge balance such as reaching different targets during activities such as sit to stand, dodging obstacles etc. Participants will play approximately 6 games for 30 minutes, 3 days a week.<br>|
| Other: Stretching and virtual reality (control)<br>The stretching group will perform stretching exercises and VR-based games 3 times a week for 8 weeks. | Behavioral: Stretching exercise<br>* Stretches of face, neck, upper extremity, trunk and lower extremity muscles including whole body stretches for 30 minutes, 3 days per week.<br>Behavioral: Virtual reality (VR)-based gaming<br>* VR games will involve games that challenge balance such as reaching different targets during activities such as sit to stand, dodging obstacles etc. Participants will play approximately 6 games for 30 minutes, 3 days a week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Balance | Balance will be tested with the Mini Balance Evaluation Systems Test(miniBESTest), involving 14 different tasks including the timed up and go test to assess static and dynamic balance. Scores range from 0 to 28 with higher scores suggesting better balance. | Baseline, post (8 week), follow-up (14 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postural stability | Postural stability will be assessed by the Biodex Balance System. | Baseline, post (8 week), follow-up (14 weeks) | 
| Endurance | The 6-minute walk test will be used as a measure of cardiovascular endurance | Baseline, post (8 week), follow-up (14 weeks) | 
| Spatiotemporal gait parameters | Spatiotemporal measures of gait will be acquired with the GAITRite™ gait mat. | Baseline, post (8 week), follow-up (14 weeks) | 
| Brain derived neurotrophic growth factor (BDNF) | Blood sample will be obtained for measuring circulating levels of brain derived neurotrophic growth factor (BDNF). | Baseline, post (8 week), follow-up (14 weeks) | 
| Corticomotor excitability | Corticomotor excitability for the tibialis anterior motor representations will be measured with single and paired pulse transcranial magnetic stimulation (TMS). | Baseline, post (8 week), follow-up (14 weeks) | 
| Spinal reflex excitability | The H reflex will be recorded for a subset of participants in the experimental group. | Baseline, post (8 week), follow-up (14 weeks) | 
| Parkinson's Disease Questionnaire (PDQ-39) | The Parkinson's disease questionnaire (PDQ-39) is a self report questionnaire that will be used to evaluate quality of life. The questionnaire consists of 39 items with each item being rated on a 5-point scale. Lower scores suggest higher quality of life. | Baseline, post (8 week), follow-up (14 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aerobic exercise, Virtual reality, Rehabilitation, Balance, Neurophysiology