Transcranial Direct Current Stimulation for Post-stroke Motor Recovery

Study Overview
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Brief Summary
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This research study is to find out if brain stimulation at different dosage level combined with an efficacy-proven rehabilitation therapy can improve arm function. The stimulation technique is called transcranial direct current stimulation (tDCS). The treatment uses direct currents to stimulate specific parts of the brain affected by stroke. The adjunctive rehabilitation therapy is called modified Constraint-Induced Movement Therapy (mCIMT). During this therapy the subject will wear a mitt on the hand of the arm that was not affected by a stroke and force to use the weak arm. The study will test 3 different doses of brain stimulation in combination with mCIMT to find out the most promising one.

Official Title
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TRANScranial Direct Current Stimulation for POst-stroke Motor Recovery - a Phase II sTudy (TRANSPORT 2)

Conditions
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Stroke, Ischemic, Motor Activity, Upper Extremity Paralysis

Intervention / Treatment
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* Device: Sham
* Device: Low dose tDCS
* Device: High dose tDCS
* Behavioral: mCIMT


Participation Criteria
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Eligibility Criteria
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Each subject must meet all of the following criteria to participate in this study: 18-80 years old; and First-ever unihemispheric ischemic stroke radiologically verified and occurred within the past 30-180 days; and >10° of active wrist extension, >10° of thumb abduction/extension, and > 10° of extension in at least 2 additional digits; and Unilateral limb weakness with a Fugl-Meyer Upper Extremity score of ≤ 54 (out of 66) to avoid ceiling effects; and An absolute difference of FM-UE scores between the two baseline assessments that is ≤ 2 points indicating stable motor impairment; if subject is not stable, then he/she will be invited for a reassessment after 7-14 days (but no more than 3 reassessments); and Pre-stroke mRS ≤2; and Signed informed consent by the subject or Legally Authorized Representative (LAR). Each Subject who meets any of the following criteria will be excluded from the study: Primary intracerebral hematoma, subarachnoid hemorrhage or bi-hemispheric or bilateral brainstem ischemic strokes; Medication use at the time of study that may interfere with tDCS, including but not limited to carbamazepine, flunarizine, sulpiride, rivastigmine, dextromethorphan; Other co-existent neuromuscular disorders (pre- or post-stroke) affecting upper extremity motor function; Other neurological disorders (pre- or post-stroke) affecting subject's ability to participate in the study; Moderate to severe cognitive impairment defined as Montreal Cognitive Assessment (MOCA) score < 18/30; History of medically uncontrolled depression or other neuro-psychiatric disorders despite medications either before or after stroke that may affect subject's ability to participate in the study; Uncontrolled hypertension despite medical treatment(s) at the time of randomization, defined as SBP≥185 mmHg or DBP≥110 mmHg (patient can be treated, reassessed and randomized later); Presence of any MRI/tDCS/TMS risk factors including but not limited to: 8a) an electrically, magnetically or mechanically activated metallic or nonmetallic implant including cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system; 8b) a non-fixed metallic part in any part of the body, including a previous metallic injury to eye; 8c) pregnancy (effects of MRI, TMS, and tDCS on the fetus are unknown); 8d) history of seizure disorder or post-stroke seizure; 8e) preexisting scalp lesion under the intended electrode placement or a bone defect or hemicraniectomy; Planning to move from the local area within the next 6 months; Life expectancy less than 6 months; Has received Botulinum toxin injection to the affected upper extremity in the past 3 months prior to randomization or expectation that Botulinum will be given to the Upper Extremity prior to the completion of the last follow-up visit; Concurrent enrollment in another investigational stroke recovery study; Doesn't speak sufficient English to comply with study procedures; Expectation that subject cannot comply with study procedures and visits.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Sham Comparator: Sham tDCS + mCIMT<br>Sham tDCS (Transcranial direct current stimulation) administers no dose or zero milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT) | Device: Sham<br>* sham group receives no active current stimulation except 15 seconds of current ramp up in the beginning and 15 seconds of current ramp up in the end of the 30-minute session to create a scalp perception to blind the subject.<br>Behavioral: mCIMT<br>* All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session<br>|
| Active Comparator: 2 mA tDCS + mCIMT<br>2 mA tDCS (Transcranial direct current stimulation) administers low dose or 2 milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT) | Device: Low dose tDCS<br>* The low dose tDCS group receives direct current stimulation at 2 mA for 30 minutes per session<br>Behavioral: mCIMT<br>* All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session<br>|
| Active Comparator: 4 mA + mCIMT<br>4 mA tDCS (Transcranial direct current stimulation) administers high dose or 4 milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT) | Device: High dose tDCS<br>* The high dose tDCS group receives direct current stimulation at 4 mA for 30 minutes per session<br>Behavioral: mCIMT<br>* All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change of Motor Impairment as Assessed by Fugl-Meyer Upper-Extremity (FM-UE) scale | The Fugl-Meyer Upper-Extremity (FM-UE) scale is a measure of motor impairment. FM-UE scale consists of a 33-item assessment which provides a global assessment of UE motor impairment. A rater observes 30 voluntary UE motions and 14 voluntary lower extremity (LE) motions, 6 tendon tap responses, and provides an ordinal rating (2=near normal ability/response, 1=partial ability, 0=unable to perform/no response). FM-UE scale is a proven scale with excellent intra-rater reliability (0.99), inter-rater reliability (0.99), test-retest reliability (0.94 -0.99), and internal consistency (0.97). | Baseline through day 15 (after the intervention) and follow-up at day 45 and 105 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change of Functional Motor Activity as assessed by Wolf Motor Function Test (WMFT) | The Wolf Motor Function Test (WMFT) is a measure of functional motor activity that quantifies upper extremity (UE) motor ability through timed and functional tasks. The WMFT consists of approximately 17 functional, strength and movement quality tasks. Each task is rated on a 6 point scale. Lower scores on the 6 point scale indicate lower functioning levels (1 = does not attempt with UE being tested, 2= UE being tested does not participate functionally, but an attempt is made to use the UE, 3= Does attempt but requires assistance of the UE not being tested, requires more than 2 attempts to complete, 4= Does attempt but may lack precision, fine coordination or fluidity, 5= Does attempt, movement similar to non-affected side but slightly slower, and 6= Does attempt and movement appears to be normal). | Baseline through day 15 (after the intervention) and follow-up at day 45 and 105 | 
| Mean Change of Patient Centered Quality of Life as Assessed by Stroke-Impact-Scale(SIS) hand subscale | The SIS hand subscale assesses how having a stroke impacts a patient's life. The SIS has 8 subscales which ask questions regarding a patient's physical limitations, memory and thinking, emotions and mood, ability to communicate, daily activities, mobility at home and in the community, use of hand most affected by stroke, and ability to participate in meaningful life activities. Each subscale item is rated on a scale from 5-1 (5= None of the time, 4=a little of the time, 3=Some of the time, 2=Most of the time, 1=All of the time) | Baseline through day 15 (after the intervention) and follow-up at day 45 and 105 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, stroke recovery, brain stimulation, transcranial direct current stimulation