Cortical Priming to Optimize Gait Rehabilitation in Stroke: a Renewal

Study Overview
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Brief Summary
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Achieving functional ambulation post stroke continues to be a challenge for stroke survivors, clinicians, and researchers. In the effort to enhance outcomes of motor training, cortical priming using brain stimulation has emerged as a promising adjuvant to conventional rehabilitation. This project focuses on the development of a long term gait rehabilitation protocol using brain stimulation to improve walking outcomes in people with stroke. The project will also aim to understand the neural mechanisms that are associated with response to the intervention.

Official Title
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Cortical Priming to Optimize Gait Rehabilitation: Renewal

Conditions
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Stroke

Intervention / Treatment
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* Other: Transcranial direct current stimulation (tDCS)
* Other: Ankle motor training
* Behavioral: High intensity interval speed based treadmill training (HIISTT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years First ever monohemispheric stroke > 3 months since onset Residual hemiparetic gait deficits (e.g. abnormal gait pattern) Able to walk for 5 minutes at self-paced speed. Handheld assistive device is acceptable. Walking speed lesser than 1.2 m/s Lower limb Fugl-Meyer Motor score between 15-30 At least 5 deg of ankle dorsiflexion necessary to perform the ankle-tracking task Exclusion Criteria: General exclusion criteria Severe osteoporosis Contracture-limiting range of motion of lower limb Score of more than 2 on the Modified Ashworth Scale (indicating increased muscle tone through ankle range of motion) Uncontrolled anti-spasticity medications during the study period Score less than 6 on the Fugl-Meyer Sensory Assessment Scale for the Lower Limb Cardiorespiratory or metabolic diseases (e.g. cardiac arrhythmia, uncontrolled hypertension or diabetes, chronic emphysema) Unhealed decubiti, persistent infection Significant cognitive or communication impairment (Mini-Mental State Examination (MMSE)<21), which could impede the understanding of the purpose of procedures of the study or prevent the patient from performing the ankle-tracking task. Lesions involving the brainstem and cerebellum Failure to pass the graded exercise stress test TMS exclusion criteria Implanted cardiac pacemaker Metal implants in the head or face Unexplained, recurring headaches History of seizures or epilepsy Currently under medication that could increase motor excitability and lower seizure threshold Skull abnormalities or fractures Concussion within the last 6 months Currently pregnant tDCS exclusion criteria Skin hypersensitivity History of contact dermatitits History of allodynia and/or hyperalgesia Any other skin or scalp condition that could be aggravated by tDCS

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Priming+HIISTT<br>Facilitatory transcranial direct current stimulation (tDCS) and ankle motor training before high intensity interval speed based treadmill training | Other: Transcranial direct current stimulation (tDCS)<br>* 1 mA tDCS<br>Other: Ankle motor training<br>* Visuomotor target tracking task<br>Behavioral: High intensity interval speed based treadmill training (HIISTT)<br>* Each treadmill session to include warm-up, high intensity speed-based intervals interleaved with active recovery, and cool down.<br>|
| Sham Comparator: Sham+HIISTT<br>Sham tDCS before high intensity interval speed based treadmill training | Behavioral: High intensity interval speed based treadmill training (HIISTT)<br>* Each treadmill session to include warm-up, high intensity speed-based intervals interleaved with active recovery, and cool down.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking speed with 10 meter walk test | Self-selected and fastest gait speed will be measured as the average of 3 trials of the 10-m walk test (10MWT). | Change from baseline to immediately after training and baseline to 3 months follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking spatiotemporal characteristics with GAITRite walkway | Spatiotemporal parameters of walking will be assessed using a 7m long pressure sensitive mat (GAITRite walkway). | Change from baseline to immediately after training and baseline to 3 months follow up | 
| Motor impairment with Fugl Meyer Lower Extremity Scale | Lower extremity impairment will be measured using the Fugl Meyer Lower Extremity Scale (FMLE), a series of tests of movement, reflex activity, coordination/speed, sensation, and range of motion. The maximum score is 34 and a high score indicates less impairment | Change from baseline to immediately after training and baseline to 3 months follow up | 
| Walking endurance with 6-minute walk test | Walking endurance will be measured using the 6-Minute Walk test. Participants will walk as far as possible within 6 minutes. | Change from baseline to immediately after training and baseline to 3 months follow up | 
| Ankle range of motion | Ankle range of motion will be measured using a wireless electrogoniometer affixed to the ankle. | Change from baseline to immediately after training and baseline to 3 months follow up | 
| Ankle motor control | The participant will track a computer-generated sinusoidal target with ankle dorsiflexion and plantarflexion in a custom-built ankle-tracking device. Accuracy of tracking the target with ankle motion will be calculated. | Change from baseline to immediately after training and baseline to 3 months follow up | 
| Balance with mini Balance Evaluations Systems Test (miniBESTest) | Balance will be tested with the Mini-BESTest, involving 14 different tasks to challenge balance. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| Aerobic capacity | Cardiopulmonary exercise tests will be performed on a motorized treadmill following an individualized protocol using standard procedures. Measures relating to peak oxygen consumption (VO2 max) will be calculated. | Change from baseline to immediately after training. | 
| Quality of Life with EuroQol-5D (EQ-5D) | Quality of life will be measured with the EuroQol-5D (EQ-5D), a questionnaire with questions designed to assess aspects of quality of life. | Change from baseline to immediately after training. | 
| Disability with Modified Rankin Scale | Global disability will be measured with the modified Rankin Scale, a simple 0-6 rating scale. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| Community ambulation with wearable sensors | Daily ambulation will be assessed using an accelerometer. | Change from baseline to immediately after training. | 
| Serum brain derived neurotrophic growth factor (BDNF) | 5 ml of blood will be collected from a vein in the participants' arms | Change from baseline to immediately after training. | 
| Corticomotor excitability using transcranial magnetic stimulation | Corticomotor excitability of the paretic and non-paretic lower limb muscles such as the tibialis anterior and soleus muscle representations will be measured with single pulse transcranial magnetic stimulation (TMS). | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| Cognitive function using Mini Mental Screening Examination | 30-point questionnaire used to capture orientation, attention, memory and language. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| Depression using Patient Health Questionnaire-9 (PHQ-9) | The 9-point questionnaire is used to measure degree of depression. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| Modified Ashworth Scale | The modified Ashworth scale is a muscle tone assessment scale used to assess the resistance experienced during passive range of motion, | Change from baseline to immediately after training and baseline to 3 months follow up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tDCS, Walking