Exercise and Transcranial Magnetic Stimulation: Increasing Brain Plasticity in Parkinson's Disease

Study Overview
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Brief Summary
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This is a feasibility and exploratory study consisting of two parts: first, a cross-sectional (one-time) biomarker measurement comparing BDNF-TrkB (Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB,) signaling and cortical plasticity in patients diagnosed with Parkinson's Disease (PD) vs. healthy controls matched by age. Second, a prospective, randomized, double blind trial of Transcranial Magnetic Stimulation (TMS) MAGSTIM Rapid2 Therapy System (TMS) (real or Sham) and aerobic exercise. This exploratory feasibility study will look at BDNF-TrkB signaling and cortical plasticity.

Detailed Description
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Twenty-four PD patients (n=24) will be randomly assigned to receive one of two interventions for a duration of two weeks. In Group 1, subjects will participate in daily sessions of sham-rTMS followed by supervised aerobic exercise (Sham rTMS+Aerobic); in Group 2, subjects will participate in a combination of rTMS and supervised aerobic exercise (Real rTMS+Aerobic). Serum BDNF-TrkB signaling in lymphocytes and TMS-based electrophysiological measures of LTP-like plasticity will be measured. A comparison of such measures in a group of patients with PD and in a group of age-matched controls (n=12) will be analyzed to establish the effect of the disease on indices of plasticity.

Official Title
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Exercise and Transcranial Magnetic Stimulation: Increasing Brain Plasticity in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Behavioral: Sham rTMS
* Other: Real rTMS
* Behavioral: Supervised aerobic exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PD according to the UK Brain Bank Criteria, confirmed by a neurologist with expertise in movement disorders; Hoehn and Yahr stage II to III; On a stable medication regimen since at least 2 weeks prior the enrolment in the study and, in the view of the treating neurologist, unlikely to require medication adjustments in the following 3-6 months. Inclusion Criteria (Healthy Controls) Male or Female; aged 35-85 Exclusion Criteria (Healthy Controls) History of seizure disorder, including febrile seizures; Neurological disorder including PD, stroke, traumatic brain injury, fainting spells or syncope of unknown cause(s); Major or unstable medical illness; Pacemakers, neurostimulators, tattoos or metal foreign bodies in the head area (dental fillings are allowed); Untreated depression, or score of >20 on Beck Depression Inventory II; Taking any of the following medications within the six weeks prior to the start of the study: imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, theophylline, calcium channel blockers, beta blockers, tadalafil, vardenafil, avanafil, and sildenafil; Diagnosis of dementia, or Montreal Cognitive Assessment (MoCA) <20; Any clinically significant abnormality on vital signs Cardiopulmonary limitations: untreated high blood pressure, history of heart insufficiency (class II-III), coronary vascular disease, angina, arrhythmia, dyspnea on exertion and asthma

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: Sham Group<br>Sham group will receive Sham rTMS+Aerobic Exercise | Behavioral: Sham rTMS<br>* Subjects will participate in daily sessions of sham-rTMS<br>Behavioral: Supervised aerobic exercise<br> <br> |
| Experimental: Group 2: Real Group<br>rTMS+Aerobic Exercise | Other: Real rTMS<br>* Subjects will participate in a combination of rTMS<br>Behavioral: Supervised aerobic exercise<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment Enrollment Numbers |  | 2 Weeks | 
| Number of enrolled subjects that remain in study |  | 2 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasticity measured by TMS-PAS25 (LTP-like plasticity biomarker) | A paired associative paradigm at 25 ms (TMS-PAS-25) to quantify cortical LTP in M1 motor cortex will be used. As well as a repetitive biphasic magnetic stimulator (Magstim Rapid2 stimulator -Magstim Co., Whitland, U.K.) with a Figure of eight coil (outer diameters: 9 cm) and apply standard protocol for LTP-like measurements. | 2 Weeks | 
| Measurements of lymphocytes |  | 2 Weeks | 
| Measurements of TrkB |  | 2 Weeks | 
| Measurements of serum BDNF |  | 2 Weeks | 
| Timed Up and Go Test |  | 2 Weeks | 
| Freezing of Gait Questionnaire (FOG-Q) |  | 2 Weeks | 
| Parkinson's Disease Quality of Life (PDQ-39) |  | 2 Weeks | 
| Parkinson's Disease Sleep Scale (PDSS) |  | 2 Weeks | 
| Frontal Function Assessment (FAB) |  | 2 Weeks | 
| LASA Physical Activity Questionnaire (LAPAQ) |  | 2 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Magnetic Stimulation, Exercise, Brain Plasticity