rTMS on Motor Function of Parkinson's Disease Patients With Different Phenotypes

Study Overview
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Brief Summary
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In this study we wondered whether patients with different phenotypes of Parkinson's disease respond differently to the protocol of repetitive transcranial magnetic stimulation (rTMS) associated with physical therapy. Furthermore, the study aims to compare the effects of rTMS protocols (high and low frequency) associated with physical therapy in PD patients with different phenotypes regarding to motor performance; bradykinesia; functional mobility; balance; quality of life; perception of improvement.

Detailed Description
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After given prior informed consent, volunteers will be classified and randomized using a website (randomization.com) by a non-involved researcher. At study beginning, volunteers will be evaluated through structured questionnaire. They will be submitted to the following evaluations: (i) Unified Parkinson's disease Rating Scale (UPDRS); (ii) Parkinson's disease Sleep Scale; (iii) Parkinson's disease questionnaire; (iv) Short version of Balance Evaluation Systems Test; (v) Timed up and go; (vi) 5-times sit to stand test; (iv) Patient Global Impression of Change Scale. The cortical activity of the patients will be assessed through electroencephalography and transcranial magnetic stimulation. Treatment - Participants will be randomly allocated to one of the following experimental protocols: (i) real high frequency rTMS + physical therapy protocol; (ii) real low frequency rTMS + physical therapy protocol; (iii) rTMS sham + physiotherapeutic protocol. The sessions will be performed five times a week for two weeks. Individuals allocated to the high frequency rTMS group will be performed the following protocol: first the coil center will be positioned over Cz for the first 1000 pulses. Then the coil will be moved to C4 and C3, where 1000 pulses will be delivered to each hemisphere. The intensity will be set to 100% of the motor threshold. The high frequency stimulation will be delivered at 10 Hz, offered in 20 50-pulse trains, with 30-second train intervals. The low frequency will be performed at 1 Hz. All groups will be treated with physical therapy immediately after rTMS.

Official Title
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Effects of rTMS Associated to Physical Therapy on Motor Function of Parkinson's Disease Patients With Different Phenotypes

Conditions
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Parkinson Disease

Intervention / Treatment
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* Combination Product: High frequency repetitive transcranial magnetic stimulation
* Combination Product: Low frequency repetitive transcranial magnetic stimulation
* Combination Product: Sham repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of PD provided by neurologist; Aged 40 or over, of both gender; Regular antiparkinsonian pharmacological treatment; With staging from I to IV on the modified Hoehn & Yahr scale. Exclusion Criteria: Prior neurological diseases Metal implant in the skull and face Pacemaker History of seizures Epilepsy Pregnancy Other disorders that affect the performance of the tests and proposed intervention Other osteomioarticular diseases in the lower limbs that interfere with performance and locomotion Submitted to previous surgical intervention for PD

Ages Eligible for Study
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Minimum Age: 40 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High frequency rTMS + physical therapy<br>The sessions will be performed five times a week for two weeks. The individuals will be performed the following protocol: first the coil center will be positioned over Cz for the first 1000 pulses. Then the coil will be moved to C4 and C3, where 1000 pulses will be delivered to each hemisphere. The intensity will be set to 100% of the motor threshold. The high frequency stimulation will be delivered at 10 Hz, offered in 20 50-pulse trains, with 30-second train intervals. After rTMS, patients will be submitted to 40 minutes of physical therapy protocol. | Combination Product: High frequency repetitive transcranial magnetic stimulation<br>* The sessions will be performed five times a week for two weeks. The individuals will be performed the following protocol: first the coil center will be positioned over Cz for the first 1000 pulses. Then the coil will be moved to C4 and C3, where 1000 pulses will be delivered to each hemisphere. The intensity will be set to 100% of the motor threshold. The high frequency stimulation will be delivered at 10 Hz, offered in 20 50-pulse trains, with 30-second train intervals. The low frequency will be performed at 1 Hz. After rTMS, patients will be submitted to 40 minutes of physical therapy protocol.<br>|
| Active Comparator: Low frequency rTMS + physical therapy<br>The sessions will be performed five times a week for two weeks. The individuals will be performed the following protocol: first the coil center will be positioned over Cz for the first 1000 pulses. Then the coil will be moved to C4 and C3, where 1000 pulses will be delivered to each hemisphere. The intensity will be set to 100% of the motor threshold. The low frequency will be performed at 1 Hz. After rTMS, patients will be submitted to 40 minutes of physical therapy protocol. | Combination Product: Low frequency repetitive transcranial magnetic stimulation<br>* The sessions will be performed five times a week for two weeks. The individuals will be performed the following protocol: first the coil center will be positioned over Cz for the first 1000 pulses. Then the coil will be moved to C4 and C3, where 1000 pulses will be delivered to each hemisphere. The intensity will be set to 100% of the motor threshold. The high frequency stimulation will be delivered at 10 Hz, offered in 20 50-pulse trains, with 30-second train intervals. The low frequency will be performed at 1 Hz. After rTMS, patients will be submitted to 40 minutes of physical therapy protocol.<br>|
| Sham Comparator: Sham rTMS + physical therapy<br>For sham stimulation, the stimulator positioned behind the patient will be turned off immediately after the determination of RMT, however, the coil will remain positioned over the patient's scalp (Cz, C3 and C4). A computer equipped with speakers will play an audio recording with the characteristic rTMS sound and no stimulation will be induced in the brain. | Combination Product: Sham repetitive transcranial magnetic stimulation<br>* For sham stimulation, the stimulator positioned behind the patient will be turned off immediately after the determination of RMT, however, the coil will remain positioned over the patient's scalp (Cz, C3 and C4). A computer equipped with speakers will play an audio recording with the characteristic rTMS sound and no stimulation will be induced in the brain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Unified Parkinson's disease Rating Scale - Session III | In the present study we will analyze the UPDRS session III which comprises 14 items with a score of 0-4 each, from best to worst motor performance (SHULMAN et al., 2010). According to UPDRS scores, patients will be classified as: (i) tremor-dominant (TD) or (ii) with postural instability and difficulty in walking (PIGD). | baseline, after 7 days, after 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on cortical excitability level | it will be evaluated through single pulse transcranial magnetic stimulation. Initially, rest motor threshold (RMT) will be determined by finding the lowest stimulator output that elicit motor evoked potential (MEP) around 50 μV (TMS Motor Threshold Assessment Tool -MTAT 2.0 - USA For RMT measure, a figure-eight coil connected to the magnetic stimulator held manually at 45 degrees from the midline, will be placed over the primary motor cortex of most and less impaired hemisphere (C3 and C4 - 10/20 System). | baseline, after 7 days, after 15 days | 
| Changes on quality of life | It will be evaluated through the score of each domain of Parkinson Disease Questionnaire (PDQ-39), a specific questionnaire for Parkinson's disease. It comprises 39 questions that assesses how often people affected by Parkinson's experience difficulties across 8 dimensions of daily living. Higher values represent a worse perception of quality of life. | baseline, after 15 days | 
| Changes on Patient Global Impression of Change Scale | The PGICS is a one-dimensional measure in which individuals rate their improvement associated with intervention on a scale of 7 items ranging from 1 = no change to 7 = Much better. | after 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease