The Effect of Multi-target Magnetic Stimulation on Freezing Gait in PD

Study Overview
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Brief Summary
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This study is a double-blinded randomized study examining the effectiveness of the multi-target magnetic stimulation treatment on Freezing of Gait (FOG) phenomenon in patients with Parkinson's disease. We hypothesize that treatment using magnetic stimulation on motor cortex combined with spinal cord will improve FOG and gait symptoms in patients with Parkinson's disease.

Detailed Description
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Patients in the Experimental group underwent ten sessions of double active magnetic stimulation with low frequency repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex of the lower leg followed by low frequency repetitive magnetic stimulation over the spinal cord, whereas patients in the Active Comparator group underwent ten sessions of single active magnetic stimulation with low frequency rTMS over the bilateral primary motor cortex of the lower leg. In addition, patients in the Sham Comparator group underwent 10 sessions of double sham rTMS on motor cortex and spinal cord. Assessments of FOG, gait function, motor symptoms and excitability of primary motor cortex motor were performed three times: at baseline, one day post intervention, one month post intervention.

Official Title
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The Effect of Multi-target Magnetic Stimulation on Freezing Gait in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Idiopathic Parkinson's disease (PD), as diagnosed by a neurologist. 2.Item 3 of the Freezing of Gait Questionnaire(FOG-Q) scored ≥1. 3.Age between 40 and 80 years old. 4.Mini-Mental State Examination score >24. 5.Ability to walk 30 meters independently. 6.Stable medication. 7.Patients experienced FOG in both medication on and off states. Exclusion Criteria: 1.Other neurological or psychiatric disorders. 2.Severe personality disorder.History of epilepsy, seizures, or convulsions. 3.History of head injury or stroke. 4.Metal remains of the skull or inside the brain (outside the oral cavity). 5.Surgeries including metallic implants or known history of metal particles in the eye, pacemakers,hearing devices transplantation, or medical pumps. 6.Severe dyskinesia, termor, cognitive, visual or auditory impairment. 7.Patients who could not complete the follow-up.

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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Accepts Healthy Volunteers

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: double active magnetic stimulation<br>the multi-target magnetic stimulation on motor cortex combined with spinal cord | Device: magnetic stimulation<br>* For Experimental Arm, active magnetic stimulation on motor cortex followed by active magnetic stimulation on spinal cord, patients underwent ten sessions of double active magnetic stimulation with low frequency repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex of the lower leg followed by low frequency repetitive magnetic stimulation over the spinal cord. For Active Comparator Arm, active magnetic stimulation on motor cortex followed by sham magnetic stimulation on spinal cord. For Sham Comparator Arm, sham magnetic stimulation on motor cortex followed by sham magnetic stimulation on spinal cord.<br>|
| Active Comparator: single active magnetic stimulation<br>the active magnetic stimulation on motor cortex and sham stimulation on spinal cord | Device: magnetic stimulation<br>* For Experimental Arm, active magnetic stimulation on motor cortex followed by active magnetic stimulation on spinal cord, patients underwent ten sessions of double active magnetic stimulation with low frequency repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex of the lower leg followed by low frequency repetitive magnetic stimulation over the spinal cord. For Active Comparator Arm, active magnetic stimulation on motor cortex followed by sham magnetic stimulation on spinal cord. For Sham Comparator Arm, sham magnetic stimulation on motor cortex followed by sham magnetic stimulation on spinal cord.<br>|
| Sham Comparator: double sham magnetic stimulation<br>the sham magnetic stimulation on motor cortex and sham stimulation on spinal cord | Device: magnetic stimulation<br>* For Experimental Arm, active magnetic stimulation on motor cortex followed by active magnetic stimulation on spinal cord, patients underwent ten sessions of double active magnetic stimulation with low frequency repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex of the lower leg followed by low frequency repetitive magnetic stimulation over the spinal cord. For Active Comparator Arm, active magnetic stimulation on motor cortex followed by sham magnetic stimulation on spinal cord. For Sham Comparator Arm, sham magnetic stimulation on motor cortex followed by sham magnetic stimulation on spinal cord.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Freezing of Gait Questionnaire (FOG-Q) | The Freezing of Gait questionnaire will be used to quantify the frequency and severity of this symptom. The score will be compared to the baseline. The minimum and maximum values of the FOG-Q are 0 and 24. A higher FOG-Q score means a worse outcome. | Assessed at baseline, one day post intervention, one month post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The motor part of the Unified Parkinson's Disease Rating Scale | The measure mainly reflects the overall severity of Parkinson's disease motor symptoms. The minimum and maximum values of the motor part of the Unified Parkinson's Disease Rating Scale are 0 and 108. A higher score means a worse outcome. | Assessed at baseline, one day post intervention, one month post intervention | 
| Gait speed | Gait speed (m/s) was evaluated at baseline, one day post intervention, one month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. | Assessed at baseline, one day post intervention, one month post intervention | 
| Stride length | Stride length (cm) was evaluated at baseline, one day post intervention, one month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. | Assessed at baseline, one day post intervention, one month post intervention | 
| Stride time variability | Stride time variability (%) was evaluated at baseline, one day post intervention, one month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. Stride time variability was expressed as coefficient of variation [CV]. | Assessed at baseline, one day post intervention, one month post intervention | 
| Double support | Double support (%) was evaluated at baseline, one day post intervention, one month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. | Assessed at baseline, one day post intervention, one month post intervention | 
| Resting motor threshold (RMT) | RMT (% TMS output intensity) is defined as the lowest intensity required to elicit MEPs of > 50 μV in at least 5 of 10 consecutive trials while the target muscle is relaxed. RMT was determined to be the nearest 1% of the maximum stimulator output. | Assessed at baseline, one day post intervention. | 
| MEP amplitude at 120% RMT intensity (AMP) | Five single stimuli were delivered to the optimal stimulation point at an intensity of 120% of RMT, and the mean peak-to-peak amplitude of the MEPs was calculated, which is the AMP (mV). | Assessed at baseline, one day post intervention. | 
| Cortical silent period (CSP) | The CSP (ms) is measured through electromyographic signal recording (EMG) on a target muscle and refers to the period of EMG silence following the elicitation of a motor-evoked potential (MEP) through a single TMS pulse delivered over the contralateral primary motor cortex. Individuals were asked to actively contract abductor pollicis brevis (APB) with 20% of the maximum force, while a single pulse with 150% of RMT was applied to the opposite primary motor cortex. We recorded the time from pulse outputting to the recovery of inhibited active contraction as CSP. The above protocol was repeated ten times, and the average value of CSP was calculated. | Assessed at baseline, one day post intervention. | 
| Short-interval intracortical inhibition (SICI) | SICI was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with a 4ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. SICI was expressed as the percentage ratio between the test and conditioning MEP. | Assessed at baseline, one day post intervention. | 
| Intracortical facilitation (ICF) | ICF was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with a 15 ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. ICF was expressed as the percentage ratio between the test and conditioning MEP. | Assessed at baseline, one day post intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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freezing of gait, Therapeutics, rTMS, spinal cord stimulation