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

Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02701647
• Other study ID #: HSEARS20140423002
• Status: Completed
• Phase: N/A
• Start date: October 2016
• Est. completion date: May 2019

Study information

• Verified date: June 2018
• Source: The Hong Kong Polytechnic University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: May 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Device:
• Repetitive 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.

Other:
• 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. 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.

Locations

Country	Name	City	State
Hong Kong	Rehabilitation Sciences	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The Hong Kong Polytechnic University

Country where clinical trial is conducted

Hong Kong, 

References & Publications (1)

Yang YR, Tseng CY, Chiou SY, Liao KK, Cheng SJ, Lai KL, Wang RY. Combination of rTMS and treadmill training modulates corticomotor inhibition and improves walking in Parkinson disease: a randomized trial. Neurorehabil Neural Repair. 2013 Jan;27(1):79-86. doi: 10.1177/1545968312451915. Epub 2012 Jul 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
Other	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.	Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
Other	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.	Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
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.	Baseline, 1 day post-intervention, 1 month post-intervention, 3 month post-intervention
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.	Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
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.	Baseline, I day post-intervention, 1 month post-intervention and 3 months post-intervention
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.	Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
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.	Baseline, 1 day post-intervention, 1 month post-intervention and 3 months post-intervention
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.	Baseline, 1 day post-intervention, 1 month post-intervention, 3 month-post intervention