Repetitive Transcranial Magnetic Stimulation for the Treatment of Freezing of Gait in Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
Freezing of gait (FOG) is a common and devastating symptom in advanced stage Parkinson's disease (PD), which contributes to falls and disability. Unfortunately, there is no effective pharmacological treatment for FOG. It is suggested that the cortex-basal ganglia circuit, especially the frontal lobe, plays an important role in the pathogenesis of FOG. Repetitive transcranial magnetic stimulation (rTMS) effects over the cortex and affects the subcortical neural circuits. Previous studies have demonstrated that rTMS can improve FOG for PD patients. In the present randomized controlled trial (RCT) study, the invastigators aim to investigate the efficiency of rTMS over different motor regions of frontal lobe. The efficacy of treatment is evaluated by the score of FOG questionnaire and FOG provoking test, and the changing of neural network shown by functional magnetic resonance imaging (FMRI). Then the effects of rTMS over different brain regions will be compared for choosing a better target. The study will provide the evidence for non-invasive neuro-modulation of Parkinson's disease with freezing of gait (PD-FOG).

Official Title
-----------------
Repetitive Transcranial Magnetic Stimulation for the Treatment of Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial

Conditions
-----------------
Parkinson Disease, Gait Disorders, Neurologic

Intervention / Treatment
-----------------
* Device: rTMS
* Device: sham stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects fulfilled the diagnosis of idiopathic Parkinson's disease according to MDS-PD criteria Hoehn & Yahr (H-Y) stage was 2 or 3 All subjects had freezing of gait which was identified by FOGQ Exclusion Criteria: cognitive impairment (MMSE score<22) or major depression (HAMD-24 score>25) severe visual and/or haring impairment significant medical or psychiatric illnesses history of deep brain stimulation (DBS) surgery or pacemaker implantation. MRI cannot be performed in those patients current treatment with medication cannot be maintained during the study

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rTMS over M1 region<br>The stimulus intensity was set to 100% of the resting motor threshold. Ten sessions of rTMS were delivered over 2 weeks, one session per day for 5 consecutive days per week. Each session consisted of 10 trains of 100 pulses at 10Hz with an inter-train interval of 40 seconds. In this group, the target of rTMS is M1 region. | Device: rTMS<br>* The device is made in London, United Kingdom<br>|
| Experimental: rTMS over supplementary motor area (SMA)<br>The stimulus intensity was set to 100% of the resting motor threshold. Ten sessions of rTMS were delivered over 2 weeks, one session per day for 5 consecutive days per week. Each session consisted of 10 trains of 100 pulses at 10Hz with an inter-train interval of 40 seconds. In this group, the target of rTMS is SMA region. | Device: rTMS<br>* The device is made in London, United Kingdom<br>|
| Sham Comparator: sham stimulation<br> | Device: sham stimulation<br>* the device of sham stimulation was MagStim MC-P-B70 placebo butterfly coil<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change of freezing of gait questionnaire (FOGQ) | a self-assessment scale for evaluating FOG severity，the minimum value is 0, the maximum value is 24, and higher scores mean a worse outcome. | through study completion, an average of 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change of freezing of gait score (FOG score) | assess the severity of FOG, the minimum value is 0, the maximum value is 36, and higher scores mean a worse outcome. | through study completion, an average of 2 weeks | 
| the change of score of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III | assess the motor ability, the minimum value is 0, the maximum value is 132, and higher scores mean a worse outcome. | through study completion, an average of 2 weeks | 
| the change of Hamilton Depression (HAMD) Scale | assess the severity of depression, the minimum value is 0, the maximum value is 76, and higher scores mean a worse outcome. | through study completion, an average of 2 weeks | 
| the change of Mini-mental State Examination (MMSE) scale | assess the severity of mental state, the minimum value is 0, the maximum value is 30, and higher scores mean a worse outcome. | through study completion, an average of 2 weeks | 
| the change of Parkinson's Disease Questionnaire (PDQ-39) | assess the quality of life, the minimum value is 0, the maximum value is 156, and higher scores mean a worse outcome. | through study completion, an average of 2 weeks | 
| functional image of the brain (FMRI) | graph theoretical analysis of the brain network | through study completion, an average of 10 days | 

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