Parkinson's Disease
Conditions
Keywords
Transcranial Magnetic Stimulation, metaplasticity, gait training
Brief summary
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
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.
Interventions
DEVICERepetitive transcranial magnetic stimulation (rTMS)
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.
OTHERTreadmill training
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.
Sponsors
The Hong Kong Polytechnic University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fastest Walking Speed | Baseline, 1 day post-intervention, 1 month post-intervention, 3 month post-intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | Baseline, I day post-intervention, 1 month post-intervention and 3 months post-intervention | 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. |
| Walking Distance in a 2 -Minute Walk Test | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | 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. |
| Mini Balance Evaluation Systems Test Scores | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | 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. |
| Timed-Up-and-Go Test (iTUG) | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | 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. |
| Dual-task Timed-Up-and-Go Test (DT-TUG) | Baseline, 1 day post-intervention, 1 month post-intervention, 3 month-post intervention | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | TMS stimuli will be applied at 10% steps between 100% to 160% RMT. 10 stimuli will be delivered at each intensity. Peak to peak amplitude of 10 motor-evoked potentials (MEPs) at each stimulus intensity will be averaged offline.The cut-off intensity is set at 75% of maximum stimulator output due to discomfort perceived by majority of the participants. MEPs will be normalised with the maximal muscle action potential (MMax), which is determined by supramaximal electrical stimulation of the fibular nerve. A scatter graph will be generated with the average amplitude of MEPs as a function of stimulation intensity. The linear trend will be added to generate the linear recruitment curve slope. |
| Short-interval-intracortical Inhibition | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | Short-interval-intracortical inhibition (SICI) is another measure of cortical inhibition. In a paired- pulse TMS paradigm, a test pulse will be adjusted to produce MEP of at least 0.5 millivolts which will be delivered preceded by a brief conditioned pulse set at a lower intensity of 80% RMT with inter-stimulus interval of 2 milliseconds. Two stimulators connected via a Bistim module ( Magstim Co.,Whitland, UK) will be used in this test. Ten conditioned MEPs and unconditioned MEPs will be obtained in a random order and were averaged for each condition. SICI is expressed as percentage of unconditioned test MEP amplitude. |
| Cortical Silent Period | Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention | Ten suprathreshold TMS stimuli (i.e. 130% RMT) will be delivered while participant performing a 20% isometric maximal contraction of Tibialis Anterior of the more affected side. Cortical silent period (CSP) measures the duration of interruption of electromyography (EMG) activity in the contracting muscle produced by TMS. CSP duration will be determined as the period between the onset of MEP and the return of baseline EMG activity measured 50 ms before the TMS stimulus. |
Countries
Hong Kong
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 25-Hz rTMS Participants received 4s train of 25-Hz repetitive Transcranial magnetic stimulation pulses with 50s inter-train intervals. Participant received 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.
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. Maximum achieved speed will be maintained followed by 0.5 km/h decrements. Participants will maintain the rest of the treadmill session with this speed or further adjustment will be made if participants are unable to maintain. Positive verbal feedback | 17 |
| 1-Hz rTMS Participants received a total of 600 1-Hz repetitive Transcranial magnetic stimulation pulses in 10 minutes for each hemisphere and a total of 1200 pulses followed by 30 minutes of treadmill training.
Treadmill training: Participants proceeded with 30 minute of treadmill training after rTMS. A safety harness without body weight support will be provided. Walking speed on treadmill was increased by 0.2km/h every 5 minutes provided that participants could tolerate the belt speed with appropriate step length and walk with good stability. The maximum achieved speed was then maintained for the rest of the session or adjusted as needed. | 17 |
| Sham rTMS Sham repetitive Transcranial magnetic stimulation was applied over the same site as for real rTMS , however, with the cables of the coil disconnected. Another figure-of-eight coil using the same stimulation parameters (intensity, time, and frequency) as 25-Hz group will be placed posterior to the subject's neck with the handle pointing backward to produce the same clicking sound effect as 25-Hz group. Sham rTMS will be followed by 30 minutes of treadmill training.
Treadmill training: Participants proceeded with 30 minute of treadmill training after rTMS. A safety harness without body weight support will be provided. Walking speed on treadmill was increased by 0.2km/h every 5 minutes provided that participants could tolerate the belt speed with appropriate step length and walk with good stability. The maximum achieved speed was then maintained for the rest of the session or adjusted as needed. | 16 |
| Total | 50 |
Baseline characteristics
| Characteristic | 25-Hz rTMS | 1-Hz rTMS | Sham rTMS | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 6 Participants | 5 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 11 Participants | 11 Participants | 35 Participants |
| Age, Continuous | 62.7 years STANDARD_DEVIATION 6.8 | 62.1 years STANDARD_DEVIATION 5.7 | 62.1 years STANDARD_DEVIATION 5.7 | 62.3 years STANDARD_DEVIATION 6 |
| daily levodopa equivalent dose | 484.2 mg/day STANDARD_DEVIATION 336.4 | 512.5 mg/day STANDARD_DEVIATION 359.9 | 493.3 mg/day STANDARD_DEVIATION 523.9 | 496.8 mg/day STANDARD_DEVIATION 404.2 |
| Disease duration (no. of years of diagnosis of PD) | 5.2 years STANDARD_DEVIATION 3.4 | 7.5 years STANDARD_DEVIATION 4.9 | 6.9 years STANDARD_DEVIATION 3.3 | 6.5 years STANDARD_DEVIATION 4 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment Hong Kong | 17 participants | 17 participants | 16 participants | 50 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 7 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 | 0 / 16 |
| other Total, other adverse events | 0 / 17 | 0 / 17 | 0 / 16 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 16 |
Outcome results
Primary
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.
Time frame: Baseline, 1 day post-intervention, 1 month post-intervention, 3 month post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | Fastest Walking Speed | Baseline | 149.5 cm/s | Standard Deviation 24.7 |
| 25-Hz rTMS | Fastest Walking Speed | 1 day Post intervention | 164.3 cm/s | Standard Deviation 26.3 |
| 25-Hz rTMS | Fastest Walking Speed | 1 month post intervention | 167.8 cm/s | Standard Deviation 26.4 |
| 25-Hz rTMS | Fastest Walking Speed | 3 month post intervention | 163.2 cm/s | Standard Deviation 31 |
| 1-Hz rTMS | Fastest Walking Speed | 3 month post intervention | 169.9 cm/s | Standard Deviation 38.7 |
| 1-Hz rTMS | Fastest Walking Speed | Baseline | 153.1 cm/s | Standard Deviation 27.3 |
| 1-Hz rTMS | Fastest Walking Speed | 1 month post intervention | 170.6 cm/s | Standard Deviation 35.6 |
| 1-Hz rTMS | Fastest Walking Speed | 1 day Post intervention | 167.3 cm/s | Standard Deviation 34 |
| Sham rTMS | Fastest Walking Speed | 3 month post intervention | 156.7 cm/s | Standard Deviation 28 |
| Sham rTMS | Fastest Walking Speed | 1 day Post intervention | 160.7 cm/s | Standard Deviation 33.3 |
| Sham rTMS | Fastest Walking Speed | 1 month post intervention | 164.6 cm/s | Standard Deviation 32.3 |
| Sham rTMS | Fastest Walking Speed | Baseline | 156.1 cm/s | Standard Deviation 30.2 |
Secondary
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.
Time frame: Baseline, 1 day post-intervention, 1 month post-intervention, 3 month-post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 3 month post intervention | 22.3 seconds | Standard Deviation 6 |
| 25-Hz rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 1 day Post intervention | 23.1 seconds | Standard Deviation 5.6 |
| 25-Hz rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 1 month post intervention | 21.8 seconds | Standard Deviation 6 |
| 25-Hz rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | Baseline | 27.9 seconds | Standard Deviation 8.8 |
| 1-Hz rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 1 month post intervention | 20.6 seconds | Standard Deviation 4.7 |
| 1-Hz rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 3 month post intervention | 20.3 seconds | Standard Deviation 4.6 |
| 1-Hz rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | Baseline | 24.0 seconds | Standard Deviation 7 |
| 1-Hz rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 1 day Post intervention | 21.1 seconds | Standard Deviation 5.2 |
| Sham rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 3 month post intervention | 23.9 seconds | Standard Deviation 3.9 |
| Sham rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | Baseline | 25.5 seconds | Standard Deviation 5.6 |
| Sham rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 1 day Post intervention | 23.4 seconds | Standard Deviation 4 |
| Sham rTMS | Dual-task Timed-Up-and-Go Test (DT-TUG) | 1 month post intervention | 23.9 seconds | Standard Deviation 3.9 |
Secondary
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.
Time frame: Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | Mini Balance Evaluation Systems Test Scores | Baseline | 21.5 score on a scale | Standard Deviation 3.4 |
| 25-Hz rTMS | Mini Balance Evaluation Systems Test Scores | 1 day post intervention | 24.2 score on a scale | Standard Deviation 2.5 |
| 25-Hz rTMS | Mini Balance Evaluation Systems Test Scores | 1 month post intervention | 23.8 score on a scale | Standard Deviation 2.8 |
| 25-Hz rTMS | Mini Balance Evaluation Systems Test Scores | 3 month post intervention | 23.4 score on a scale | Standard Deviation 3 |
| 1-Hz rTMS | Mini Balance Evaluation Systems Test Scores | 3 month post intervention | 24.1 score on a scale | Standard Deviation 2.6 |
| 1-Hz rTMS | Mini Balance Evaluation Systems Test Scores | Baseline | 21.8 score on a scale | Standard Deviation 2.7 |
| 1-Hz rTMS | Mini Balance Evaluation Systems Test Scores | 1 month post intervention | 23.5 score on a scale | Standard Deviation 2.5 |
| 1-Hz rTMS | Mini Balance Evaluation Systems Test Scores | 1 day post intervention | 23.8 score on a scale | Standard Deviation 2.7 |
| Sham rTMS | Mini Balance Evaluation Systems Test Scores | 3 month post intervention | 23.0 score on a scale | Standard Deviation 2.4 |
| Sham rTMS | Mini Balance Evaluation Systems Test Scores | 1 day post intervention | 22.4 score on a scale | Standard Deviation 2.2 |
| Sham rTMS | Mini Balance Evaluation Systems Test Scores | 1 month post intervention | 22.8 score on a scale | Standard Deviation 2.5 |
| Sham rTMS | Mini Balance Evaluation Systems Test Scores | Baseline | 21.7 score on a scale | Standard Deviation 2.8 |
Secondary
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.
Time frame: Baseline, I day post-intervention, 1 month post-intervention and 3 months post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | Baseline | 27.9 score on a scale | Standard Deviation 10.5 |
| 25-Hz rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 1 day Post intervention | 19.9 score on a scale | Standard Deviation 8.5 |
| 25-Hz rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 1 month post intervention | 20.8 score on a scale | Standard Deviation 8.9 |
| 25-Hz rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 3 month post intervention | 22.5 score on a scale | Standard Deviation 10.1 |
| 1-Hz rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 3 month post intervention | 21.9 score on a scale | Standard Deviation 7.8 |
| 1-Hz rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | Baseline | 27.1 score on a scale | Standard Deviation 9.6 |
| 1-Hz rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 1 month post intervention | 22.5 score on a scale | Standard Deviation 7.3 |
| 1-Hz rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 1 day Post intervention | 22.2 score on a scale | Standard Deviation 7.5 |
| Sham rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 3 month post intervention | 27.3 score on a scale | Standard Deviation 8 |
| Sham rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 1 day Post intervention | 27.9 score on a scale | Standard Deviation 9 |
| Sham rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | 1 month post intervention | 27.9 score on a scale | Standard Deviation 10.1 |
| Sham rTMS | the Motor Section of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) | Baseline | 29.7 score on a scale | Standard Deviation 10.6 |
Secondary
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.
Time frame: Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | Timed-Up-and-Go Test (iTUG) | Baseline | 20.8 seconds | Standard Deviation 4 |
| 25-Hz rTMS | Timed-Up-and-Go Test (iTUG) | 1 day Post intervention | 18.4 seconds | Standard Deviation 2.8 |
| 25-Hz rTMS | Timed-Up-and-Go Test (iTUG) | 1 month post intervention | 17.7 seconds | Standard Deviation 2.9 |
| 25-Hz rTMS | Timed-Up-and-Go Test (iTUG) | 3 month post intervention | 17.9 seconds | Standard Deviation 2.8 |
| 1-Hz rTMS | Timed-Up-and-Go Test (iTUG) | 3 month post intervention | 16.6 seconds | Standard Deviation 2.3 |
| 1-Hz rTMS | Timed-Up-and-Go Test (iTUG) | Baseline | 18.3 seconds | Standard Deviation 2.5 |
| 1-Hz rTMS | Timed-Up-and-Go Test (iTUG) | 1 month post intervention | 17.1 seconds | Standard Deviation 2.3 |
| 1-Hz rTMS | Timed-Up-and-Go Test (iTUG) | 1 day Post intervention | 17.1 seconds | Standard Deviation 2.7 |
| Sham rTMS | Timed-Up-and-Go Test (iTUG) | 3 month post intervention | 18.4 seconds | Standard Deviation 2.1 |
| Sham rTMS | Timed-Up-and-Go Test (iTUG) | 1 day Post intervention | 18.0 seconds | Standard Deviation 2.1 |
| Sham rTMS | Timed-Up-and-Go Test (iTUG) | 1 month post intervention | 17.9 seconds | Standard Deviation 1.8 |
| Sham rTMS | Timed-Up-and-Go Test (iTUG) | Baseline | 19.3 seconds | Standard Deviation 2.5 |
Secondary
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.
Time frame: Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | Walking Distance in a 2 -Minute Walk Test | Baseline | 147.4 meter | Standard Deviation 29.8 |
| 25-Hz rTMS | Walking Distance in a 2 -Minute Walk Test | 1 day post intervention | 160.4 meter | Standard Deviation 28 |
| 25-Hz rTMS | Walking Distance in a 2 -Minute Walk Test | 1 month post intervention | 166.3 meter | Standard Deviation 29.7 |
| 25-Hz rTMS | Walking Distance in a 2 -Minute Walk Test | 3 month post intervention | 163.1 meter | Standard Deviation 30.7 |
| 1-Hz rTMS | Walking Distance in a 2 -Minute Walk Test | 3 month post intervention | 166.8 meter | Standard Deviation 31.2 |
| 1-Hz rTMS | Walking Distance in a 2 -Minute Walk Test | Baseline | 144.7 meter | Standard Deviation 31.3 |
| 1-Hz rTMS | Walking Distance in a 2 -Minute Walk Test | 1 month post intervention | 167.9 meter | Standard Deviation 29.7 |
| 1-Hz rTMS | Walking Distance in a 2 -Minute Walk Test | 1 day post intervention | 164.9 meter | Standard Deviation 29.8 |
| Sham rTMS | Walking Distance in a 2 -Minute Walk Test | 3 month post intervention | 160.5 meter | Standard Deviation 28.9 |
| Sham rTMS | Walking Distance in a 2 -Minute Walk Test | 1 day post intervention | 157.3 meter | Standard Deviation 31.7 |
| Sham rTMS | Walking Distance in a 2 -Minute Walk Test | 1 month post intervention | 157.9 meter | Standard Deviation 29.7 |
| Sham rTMS | Walking Distance in a 2 -Minute Walk Test | Baseline | 148.7 meter | Standard Deviation 25 |
Other Pre-specified
Cortical Silent Period
Ten suprathreshold TMS stimuli (i.e. 130% RMT) will be delivered while participant performing a 20% isometric maximal contraction of Tibialis Anterior of the more affected side. Cortical silent period (CSP) measures the duration of interruption of electromyography (EMG) activity in the contracting muscle produced by TMS. CSP duration will be determined as the period between the onset of MEP and the return of baseline EMG activity measured 50 ms before the TMS stimulus.
Time frame: Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
Population: 1 discarded data due to poor quality of data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | Cortical Silent Period | Baseline | 176.5 milliseconds | Standard Deviation 50 |
| 25-Hz rTMS | Cortical Silent Period | 1 day Post intervention | 194.4 milliseconds | Standard Deviation 53.2 |
| 25-Hz rTMS | Cortical Silent Period | 1 month post intervention | 190.1 milliseconds | Standard Deviation 54.5 |
| 25-Hz rTMS | Cortical Silent Period | 3 month post intervention | 175.9 milliseconds | Standard Deviation 43.2 |
| 1-Hz rTMS | Cortical Silent Period | 3 month post intervention | 154.6 milliseconds | Standard Deviation 46 |
| 1-Hz rTMS | Cortical Silent Period | Baseline | 164.6 milliseconds | Standard Deviation 39.8 |
| 1-Hz rTMS | Cortical Silent Period | 1 month post intervention | 160.1 milliseconds | Standard Deviation 41.1 |
| 1-Hz rTMS | Cortical Silent Period | 1 day Post intervention | 180.6 milliseconds | Standard Deviation 39.1 |
| Sham rTMS | Cortical Silent Period | 3 month post intervention | 182.9 milliseconds | Standard Deviation 35 |
| Sham rTMS | Cortical Silent Period | 1 day Post intervention | 175.1 milliseconds | Standard Deviation 46.6 |
| Sham rTMS | Cortical Silent Period | 1 month post intervention | 189.2 milliseconds | Standard Deviation 37.6 |
| Sham rTMS | Cortical Silent Period | Baseline | 183.9 milliseconds | Standard Deviation 38.9 |
Other Pre-specified
Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve)
TMS stimuli will be applied at 10% steps between 100% to 160% RMT. 10 stimuli will be delivered at each intensity. Peak to peak amplitude of 10 motor-evoked potentials (MEPs) at each stimulus intensity will be averaged offline.The cut-off intensity is set at 75% of maximum stimulator output due to discomfort perceived by majority of the participants. MEPs will be normalised with the maximal muscle action potential (MMax), which is determined by supramaximal electrical stimulation of the fibular nerve. A scatter graph will be generated with the average amplitude of MEPs as a function of stimulation intensity. The linear trend will be added to generate the linear recruitment curve slope.
Time frame: Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
Population: 2 sets of discarded data due to poor quality
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | Baseline | 0.51 millivolts / % maximum stimulator output | Standard Deviation 0.3 |
| 25-Hz rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 1 day Post intervention | 0.58 millivolts / % maximum stimulator output | Standard Deviation 0.36 |
| 25-Hz rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 1 month post intervention | 0.70 millivolts / % maximum stimulator output | Standard Deviation 0.57 |
| 25-Hz rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 3 month post intervention | 0.74 millivolts / % maximum stimulator output | Standard Deviation 0.47 |
| 1-Hz rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 3 month post intervention | 0.70 millivolts / % maximum stimulator output | Standard Deviation 0.41 |
| 1-Hz rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | Baseline | 0.53 millivolts / % maximum stimulator output | Standard Deviation 0.39 |
| 1-Hz rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 1 month post intervention | 0.63 millivolts / % maximum stimulator output | Standard Deviation 0.3 |
| 1-Hz rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 1 day Post intervention | 0.64 millivolts / % maximum stimulator output | Standard Deviation 0.37 |
| Sham rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 3 month post intervention | 0.58 millivolts / % maximum stimulator output | Standard Deviation 0.45 |
| Sham rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 1 day Post intervention | 0.52 millivolts / % maximum stimulator output | Standard Deviation 0.4 |
| Sham rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | 1 month post intervention | 0.59 millivolts / % maximum stimulator output | Standard Deviation 0.43 |
| Sham rTMS | Gradient of the Recruitment Curve ( Also Known as Stimulus-response Curve) | Baseline | 0.61 millivolts / % maximum stimulator output | Standard Deviation 0.32 |
Other Pre-specified
Short-interval-intracortical Inhibition
Short-interval-intracortical inhibition (SICI) is another measure of cortical inhibition. In a paired- pulse TMS paradigm, a test pulse will be adjusted to produce MEP of at least 0.5 millivolts which will be delivered preceded by a brief conditioned pulse set at a lower intensity of 80% RMT with inter-stimulus interval of 2 milliseconds. Two stimulators connected via a Bistim module ( Magstim Co.,Whitland, UK) will be used in this test. Ten conditioned MEPs and unconditioned MEPs will be obtained in a random order and were averaged for each condition. SICI is expressed as percentage of unconditioned test MEP amplitude.
Time frame: Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
Population: unable to perform procedure due to small MEPS values for 5 participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25-Hz rTMS | Short-interval-intracortical Inhibition | 1 month post intervention | 42.0 percentage of Unconditioned MEPs | Standard Deviation 26.9 |
| 25-Hz rTMS | Short-interval-intracortical Inhibition | 3 month post intervention | 50.8 percentage of Unconditioned MEPs | Standard Deviation 22.8 |
| 25-Hz rTMS | Short-interval-intracortical Inhibition | 1 day Post intervention | 44.4 percentage of Unconditioned MEPs | Standard Deviation 23 |
| 25-Hz rTMS | Short-interval-intracortical Inhibition | Baseline | 56.4 percentage of Unconditioned MEPs | Standard Deviation 27 |
| 1-Hz rTMS | Short-interval-intracortical Inhibition | Baseline | 49.4 percentage of Unconditioned MEPs | Standard Deviation 24.1 |
| 1-Hz rTMS | Short-interval-intracortical Inhibition | 1 day Post intervention | 51.4 percentage of Unconditioned MEPs | Standard Deviation 28.2 |
| 1-Hz rTMS | Short-interval-intracortical Inhibition | 3 month post intervention | 60.7 percentage of Unconditioned MEPs | Standard Deviation 39.2 |
| 1-Hz rTMS | Short-interval-intracortical Inhibition | 1 month post intervention | 62.6 percentage of Unconditioned MEPs | Standard Deviation 31.7 |
| Sham rTMS | Short-interval-intracortical Inhibition | 3 month post intervention | 74.3 percentage of Unconditioned MEPs | Standard Deviation 30.2 |
| Sham rTMS | Short-interval-intracortical Inhibition | Baseline | 62.2 percentage of Unconditioned MEPs | Standard Deviation 33.1 |
| Sham rTMS | Short-interval-intracortical Inhibition | 1 day Post intervention | 76.5 percentage of Unconditioned MEPs | Standard Deviation 49.8 |
| Sham rTMS | Short-interval-intracortical Inhibition | 1 month post intervention | 89.8 percentage of Unconditioned MEPs | Standard Deviation 62.9 |