Efficacy of rTMS and tDCS as Adjunctive Rehabilitation for Cerebrovascular Disease-related Gait Dysfunction

Study Overview
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Brief Summary
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This study was a prospective, randomized, single-blind, parallel-controlled, multicenter clinical study to evaluate the efficacy and safety of repetitive transcranial magnetic stimulation and transcranial direct current stimulation assisted rehabilitation in the treatment of cerebrovascular disease-related gait disorders.

Detailed Description
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This study was a prospective, randomized, single-blind, parallel-controlled, multicenter clinical study. The main purpose was to evaluate the efficacy and safety of repetitive transcranial magnetic stimulation and transcranial direct current stimulation assisted rehabilitation in the treatment of cerebrovascular disease-related gait disorders. The secondary objective was to assess the effects of these two types of neuromodulation on cognitive, emotional, and daily living abilities.

Official Title
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Efficacy of Repetitive Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation as Adjunctive Rehabilitation for Cerebrovascular Disease-related Gait Dysfunction

Conditions
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Repetitive Transcranial Magnetic Stimulation, Transcranial Direct Current Stimulation, Cerebrovascular Disease, Gait Dysfunction, Neurologic

Intervention / Treatment
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* Device: Active rTMS
* Device: Sham rTMS
* Device: Active tDCS
* Device: Sham tDCS
* Other: Walking training
* Other: Cognition training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group A: Gait Dysfunction of Hemiplegia Age ≥ 35 years old, ≤ 75 years old; There was a cerebral infarction event in the past ≥ 2 months, leaving unilateral lower extremity paralysis, muscle strength IV to V- grade; Brunnstrom staging: lower limb of paralysis (IV-V grade), lower limb of healthy side (IV-V grade), upper limbs (IV-V grade), hands (IV-V grade); Able to stand for 5 minutes without assistance, without gait aid, and to walk independently for 5 minutes without stopping; Mini-mental state examination (MMSE) > 17 points, able to complete cognitive and gait assessments. Group B: Frontal Gait Dysfunction Age ≥ 35 years old, ≤ 75 years old; Meet the frontal gait characteristics: a) Balance dysfunction: wide step base, trunk swing, increased fall, decreased trunk movement control, and autonomous activity dysfunction; b) difficulty in starting, dragging and freezing; c) without limb ataxia, dysarthria, nystagmus, decreased facial expression, decreased upper limb joint activity, upper motor neuron impaired signs, and resting tremor; There was a cerebral infarction event ≥ 2 months, or asymptomatic stroke event but the head MRI suggested single or multiple lacunar infarction or ischemic lesion (diameter ≤ 2cm); limb muscle strength V- to V grade, and the muscle strength of both limbs is the same; Able to stand for 5 minutes without assistance, without gait aid, to walk independently for 5 minutes; Able to complete cognitive and gait assessments. Exclusion Criteria: Other gait abnormalities caused by other diseases, such as Parkinson's disease, hydrocephalus, cerebellar disease, vestibular system disease, extrapyramidal abnormalities, abnormalities of proprioceptive sensibility, visual abnormalities, auditory abnormalities, peripheral nerves and musculoskeletal diseases; Symptomatic cerebral infarction <2 months; Severe nervous system diseases, such as previous cerebral hemorrhage, history of subarachnoid hemorrhage, craniocerebral trauma, cerebral vascular malformation, brain tumor, central nervous system infection, demyelinating disease, epilepsy, myelopathy, etc.; Severe cognitive impairment, major depression, and aphasia disable to finish the cognitive and gait assessments; serious cardiovascular, pulmonary, blood, rheumatism and other complications, pregnancy; Metal implants such as pacemakers or cochlear implants; Taking drugs that affect cortical excitability: such as antiepileptic drugs, sedation, benzodiazepines, antidepressants, dopamine, amphetamines, etc.; long-term heavy drinking: the alcohol content of men drinking more than 168g per week, women more than 112g; Neurological rehabilitation treatment was received within 1 month before the start of the trial.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 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 |
| --- | --- |
| Active Comparator: Group A - Active<br>Active rTMS for Gait Dysfunction of Hemiplegia | Device: Active rTMS<br>* 4-week (5 days per week) active rTMS (90%rMT, M1, 10Hz for 10s, 50s interval, 20 trains)<br>Other: Walking training<br>* 4-week (5 days per week) walking training<br>|
| Sham Comparator: Group A - Sham<br>Sham rTMS for Gait Dysfunction of Hemiplegia | Device: Sham rTMS<br>* 4-week (5 days per week) sham rTMS<br>Other: Walking training<br>* 4-week (5 days per week) walking training<br>|
| Active Comparator: Group B - Active<br>Active tDCS for Frontal Gait Dysfunction | Device: Active tDCS<br>* 4-week (5 days per week) active tDCS (2mA, DLPFC, 20 min)<br>Other: Walking training<br>* 4-week (5 days per week) walking training<br>Other: Cognition training<br>* 4-week (5 days per week) cognition training<br>|
| Sham Comparator: Group B - Sham<br>Sham tDCS for Frontal Gait Dysfunction | Device: Sham tDCS<br>* 4-week (5 days per week) sham tDCS<br>Other: Walking training<br>* 4-week (5 days per week) walking training<br>Other: Cognition training<br>* 4-week (5 days per week) cognition training<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Velocity of 10m walking test | Velocity of 10m walking test (10MWT) according to the video | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 10m walking test | Step width, step size, step frequency of 10m walking test (10MWT) according to the video | 12 weeks | 
| Turn time of time up and go test | Total time, pace, standing time, turn time of time up and go test (TUGT) according to the video | 12 weeks | 
| Dual-task walking | Pace, step width, step size, step frequency, dual task cost of dual-task walking (DTW) according to the video | 12 weeks | 
| Tinetti Balance and Gait Analysis | Gait evaluation according to Tinetti Balance and Gait Analysis (Full score: 28. score >= 19 indicates high risk of fall.) | 12 weeks | 
| Mini-mental state examination (MMSE) | Cognition evaluation according to Mini-mental state examination (Full score: 30. score <24 indicates cognitive impairment. ) | 12 weeks | 
| Montreal cognitive assessment (MoCA) | Cognition evaluation according to Montreal cognitive assessment (Full score: 30. score <26 indicates cognitive impairment. | 12 weeks | 
| Symbol digit modalities test (SDMT) | Attention evaluation according to Symbol digit modalities test (Counting number of right modalities in 90s. ) | 12 weeks | 
| Color word test (CWT) | Execution evaluation according to Color word test (Counting number of right ones. ) | 12 weeks | 
| Hamilton depression scale (HAMD) | Mood evaluation according to Hamilton depression scale (Score >7 indicates possible depression.) | 12 weeks | 
| Instrumental activities of daily living (IADL) | Daily living ability evaluation according to Instrumental activities of daily living (Full score: 24. Higher score indicates higher independence. ) | 12 weeks |