rTMS for the Treatment of Freezing of Gait in Parkinson's Disease

Study Overview
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Brief Summary
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This study is a double blind comparative study examining the effectiveness of the rTMS treatment on Freezing of Gait (FOG) in patients with Parkinson's disease (PD). The investigators hypothesize that treatment with rTMS on supplemental motor area will improve gait quality and decrease the frequency of FOG in PD patients.

Detailed Description
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Freezing of gait (FOG) is a common and debilitating symptom in patients with Parkinson's disease (PD), characterized by sudden and brief episodes of inability to produce effective forward stepping. FOG is a major risk factor for falls, and greatly contributes to reduced mobility and quality of daily life. Treatment of FOG has been perceived as a very challenging task. Although various treatment approaches exist, including pharmacological and surgical options, evidence is inconclusive for many approaches and no clear treatment protocols are available until now. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neural modulation technique, has been closely applied as a treatment for various neurologic and psychiatric disorders. A recent meta-analysis demonstrated that rTMS could improve motor symptoms for PD patients with a moderate effect size. To date, however, only few rTMS studies have focused on its efficacy on FOG in patients with parkinsonism, and most of them targeted the primary motor cortex or dorsolateral prefrontal cortex . Even though some evidence indicates the involvement of the SMA in FOG, no report has described the SMA rTMS in PD patients with FOG. Moreover, few studies combined functional magnetic resonance imaging (fMRI) and rTMS to unravel the mechanism of its beneficial effects. To address these issues, the investigators conducted a randomized, double-blind, sham-controlled study to explore the efficiency of SMA-rTMS on FOG in PD patients.

Official Title
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Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Freezing of Gait in Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Device: High-frequency rTMS
* Device: Sham rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic PD patients. Presenting with FOG. The mini-mental state examination questionnaire score above 24 points. Exclusion Criteria: Other neurological or psychiatric disorders. History of epilepsy, seizures or convulsions. Metal implantation. History of exposure to rTMS in the past (to minimizing risk of unblinding sham condition).

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-frequency rTMS<br>Patients randomized to this group will receive rTMS delivering over the supplementary motor area (SMA). Each treatment consists 1000 pulses (5-second burst of 10Hz rTMS, repeated 20 times at every minute ).Stimulus intensity is 90% of resting motor threshold. A figure-of-8 coil is connected to a biphasic magnetic stimulator, and the induced current is perpendicular to the midline. | Device: High-frequency rTMS<br>* It is delivered at a 5-second burst of 10Hz stimuli, repeated 20 times at every minute. Each treatment contains a total of 1000 pulses. Stimulus intensity is 90% of resting motor threshold. The SMA stimulation will be given using a coil centered at points 3-cm anterior to the leg motor area in the sagittal midline.<br>|
| Sham Comparator: Sham rTMS<br>Patients randomized to this group will receive the sham rTMS. The procedure is same as used in patients receiving experimental rTMS, except that the coil is angled 90° away. | Device: Sham rTMS<br>* The procedure will be same as the high-frequency rTMS except that the coil is 90° angled away.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of the New Freezing of Gait Questionnaire (NFOGQ) Score | NFOGQ ranges from 0-24 points. It is used to quantify changes of the FOG frequency and severity. Higher scores mean a worse outcome. | Pre-treatment, post-treatment 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor Subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) | The motor subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale evaluates the overall motor symptoms in PD, ranging from 0-112 points. Higher scores mean a worse outcome. | Pre-treatment, post-treatment 4 weeks | 
| Cadence | To assess the changes of straight walking function. | Pre-treatment, post-treatment 4 weeks | 
| Turning Duration | To assess the changes of turning function. | Pre-treatment, post-treatment 4 weeks | 
| Changes of Brain Functional Connectivity. | functional connectivity will be assessed using fMRI, which can help understand the neural mechanism of the rTMS treatment. Using the baseline scans, the imaging biomarkers for freezing of gait and Parkinson's disease were developed by contrasting the connectivity profiles of patients with freezing of gait to those without freezing of gait and normal controls, respectively. These two biomarkers were then interrogated to assess the rTMS effects on connectivity patterns. | Pre-treatment, post-treatment at 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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freezing of gait, rTMS, fMRI