Effects of Combined rTMS and Treadmill Training in People With Parkinson's Disease

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether the beneficial effect of treadmill training on people with Parkinson's disease can be enhanced by high- and low-frequency repetitive transcranial magnetic stimulation (rTMS).

Detailed Description
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This is a randomised placebo-controlled trial. Fifty-one participants with Parkinson's disease (PD) will be recruited from the Hong Kong PD association, a self-help group and movement disorders clinic of 3 local hospitals. Written informed consent in accordance with the Declaration of Helsinki will be obtained from all participants. Eligible participants will be randomly assigned into one of the three groups: 1Hz-TT, 25Hz-TT, and sham-TT upon recruitment. Randomisation will be generated by a computer program and group assignment will be blinded to both participants and assessor. Participant will receive either 1-Hz, 25-Hz, or sham rTMS which will last for about 20 minutes followed by 30 minutes treadmill walking training for 12 sessions, 4 times per week for 3 weeks. All assessments will be conducted 1 week before intervention and 1 day after completion of intervention, after 1-month training and at 3-month post training. The sample size calculation is based on the significant findings of the gait speed reported by Yang et al (2013). A two-way repeated measures ANOVA design with between-subject group effect (3 levels) and within-subject time effect (4 levels) determines that 15 subjects per group are required to achieve 85% power to test the interaction effect between groups and time effect with a 5% significance level and the effect size is 0.2. By assuming 10% dropout rate, 17 subjects will be required per group.

Official Title
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Repetitive Transcranial Magnetic Stimulation Promotes Gait Training in People With Parkinson's Disease - a Randomised Controlled Trial

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Device: Repetitive transcranial magnetic stimulation (rTMS)
* Other: Treadmill training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with idiopathic Parkinson's disease by a neurologist had been stable on anti-Parkinsonian medication able to walk independently for 30 meters Exclusion Criteria: severe co-morbidity that may interfere with their ability to participate including significant orthopaedic or rheumatological conditions or disorders of peripheral nervous systems that may interfere with mobility or balance performance a diagnosis of neurological disease other than PD a history of psychiatric disorders the impossibility of inducing motor evoked potentials (MEPs) a score of less than 24 on the Mini-Mental State Examination contraindication to TMS including personal or family history of seizure disorder, metal in the head, implants of medical devices such as cardiac pacemakers or medical pumps, females subjects who are pregnant, a history of neurosurgery subjects with irrepressible tremor and / or dyskinesia

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: 25Hz-TT<br>Participants will receive 4s train of 25-Hz rTMS pulses with 50s inter-train interval, with an intensity of 80% resting motor threshold (RMT). Participant will receive a total of 600 rTMS pulses in 6 minutes for each hemisphere and a total of 1200 pulses followed by 30 minutes of treadmill training. | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* Repetitive TMS (rTMS) is a painless and non-invasive technique for activation of cerebral cortex based on the principle of electromagnetic induction of an electric field in the brain. rTMS will be delivered to the scalp over the leg area of the bilateral motor cortex by using a Magstim Rapid magnetic stimulator. (Magstim Company, Whitland, UK) and 90 mm double cone coil.<br>Other: Treadmill training<br>* Participants will proceed to 30 minute of treadmill training after rTMS. A safety harness without body weight support will be provided. 80% of participant's over ground maximum walking speed will be halved and used for warm-up. After warming up, walking speed will be increased by 0.2 km/h every 5 minutes. Progression will be given if patients could tolerate the belt speed with appropriate step length and walk with good stability for 5 minutes. Participants will maintain the maximum speed achieved for the rest of the session or adjusted as needed. Positive verbal feedback will be given to encourage large strides and upright posture during training. The participants will be instructed to walk on treadmill without holding onto the handrails if possible. Participants will perform warm up and cool down exercise to minimize training related-injury.<br>|
| Experimental: 1Hz-TT<br>Participants will receive a total of 600 1-Hz rTMS pulses in 10 minutes for each hemisphere and a total of 1200 pulses ,with an intensity of 80% RMT, followed by 30 minutes of treadmill training. | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* Repetitive TMS (rTMS) is a painless and non-invasive technique for activation of cerebral cortex based on the principle of electromagnetic induction of an electric field in the brain. rTMS will be delivered to the scalp over the leg area of the bilateral motor cortex by using a Magstim Rapid magnetic stimulator. (Magstim Company, Whitland, UK) and 90 mm double cone coil.<br>Other: Treadmill training<br>* Participants will proceed to 30 minute of treadmill training after rTMS. A safety harness without body weight support will be provided. 80% of participant's over ground maximum walking speed will be halved and used for warm-up. After warming up, walking speed will be increased by 0.2 km/h every 5 minutes. Progression will be given if patients could tolerate the belt speed with appropriate step length and walk with good stability for 5 minutes. Participants will maintain the maximum speed achieved for the rest of the session or adjusted as needed. Positive verbal feedback will be given to encourage large strides and upright posture during training. The participants will be instructed to walk on treadmill without holding onto the handrails if possible. Participants will perform warm up and cool down exercise to minimize training related-injury.<br>|
| Sham Comparator: Sham-TT<br>Sham rTMS will be applied over the same site as for real rTMS, however, with the cable of the coil disconnected. Another figure-of-eight coil using the same stimulation parameters (intensity, time, and frequency) as per 25Hz-TT group will be placed posterior to the subject's neck with the handle pointing backward to produce the same clicking sound effect. Sham rTMS will be followed by 30 minutes of treadmill training. | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* Repetitive TMS (rTMS) is a painless and non-invasive technique for activation of cerebral cortex based on the principle of electromagnetic induction of an electric field in the brain. rTMS will be delivered to the scalp over the leg area of the bilateral motor cortex by using a Magstim Rapid magnetic stimulator. (Magstim Company, Whitland, UK) and 90 mm double cone coil.<br>Other: Treadmill training<br>* Participants will proceed to 30 minute of treadmill training after rTMS. A safety harness without body weight support will be provided. 80% of participant's over ground maximum walking speed will be halved and used for warm-up. After warming up, walking speed will be increased by 0.2 km/h every 5 minutes. Progression will be given if patients could tolerate the belt speed with appropriate step length and walk with good stability for 5 minutes. Participants will maintain the maximum speed achieved for the rest of the session or adjusted as needed. Positive verbal feedback will be given to encourage large strides and upright posture during training. The participants will be instructed to walk on treadmill without holding onto the handrails if possible. Participants will perform warm up and cool down exercise to minimize training related-injury.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fastest Walking Speed | Each participant is instructed to walk for 14 meters at their fastest walking speed for three trials. The time taken for the middle 10 meter was recorded. The average of three trials is used for analysis. | Baseline, 1 day post-intervention, 1 month post-intervention, 3 month post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timed-Up-and-Go Test (iTUG) | Participants are instructed to stand up from a chair and walk for 7 meters walkway and return back to the chair turn around and sit down. Time and gait parameters during TUG were captured by the valid and reliable APDM system, which is a wearable gait and balance analysis system. | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | 
| the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | MDS-UPDRS III is a valid and reliable clinical test, will be used to evaluate severity of motor symptoms of PD. There are total of 27 items including tremor, rigidity, bradykinesia, postural instability and gait performance. Each item scores from 0-4, with 0 indicates no disability and 4 maximum disabled with total score(s) ranges from 0 to 132. | Baseline, I day post-intervention, 1 month post-intervention and 3 months post-intervention | 
| Walking Distance in a 2 -Minute Walk Test | The 2 minute walk test will be conducted along a 20 m x 2 m hallway. A line is marked at each end of the walkway to indicate where the person is to turn. Participants will be instructed to  walk as far as possible in 2 minutes. They will be given standardised encouragement at 60 and 90 seconds during walk. Distance walked will be recorded to the nearest meter. | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | 
| Mini Balance Evaluation Systems Test Scores | Balance performance of participants will be assessed in 4 domains namely anticipatory postural adjustments, postural responses, sensory orientation and gait stability. Each item is rated from 0-2 with a total scores of 28. The Total scores range from 0-28, with higher scores indicate better dynamic balance. | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | 
| Dual-task Timed-Up-and-Go Test (DT-TUG) | For DT-TUG, participants were instructured to repeat the TUG procedure while performing a serial three substraction. Time taken to complete DT-TUG and accuracy of digital counting was recorded. One practice trial was given prior to both TUG and DT-TUG testing and average performance of three trials was used for analysis. | Baseline, 1 day post-intervention, 1 month post-intervention, 3 month-post intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Magnetic Stimulation, metaplasticity, gait training