Electric Field Navigated 1hz Rtms for Post-stroke Motor Recovery Trial

Study Overview
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Brief Summary
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A prospective, multi-center, randomized, sham-controlled, blinded study combining active Nexstim NBS-guided 1Hz rTMS or sham-rTMS targeting the healthy hemisphere with standardized task oriented rehabilitation will be conducted in patients with post-stroke motor impairment of the upper limb. The therapy will be provided for 6 weeks and primary outcome assessed 6 months later.

Official Title
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A Prospective, Multi-center, Randomized, Sham-controlled Trial to Determine the Therapeutic Effects of Navigation Guided 1 hz Rtms Administered to the Contralesional Hemisphere as Adjuvant to Task-oriented Rehabilitation in Patients With Ischemic Stroke

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Device: Nexstim NBS guided active rTMS
* Device: Nexstim NBS guided sham rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age An ischemic stroke suffered 3-12 months prior to the study No other known brain abnormalities by history; A one-sided stroke resulting in upper extremity paresis A Chedoke-McMaster Stroke Assessment arm stage and hand stage of 3-6 for the affected limb Exclusion Criteria: Implanted metallic parts of implanted electronic devices, including pacemakers, defibrillators, or implant medication pump; Pregnant or trying to become pregnant; Lack of pregnancy established in females of child-bearing potential by a negative urine pregnancy test at screening. Active alcohol abuse, illicit drug use or drug abuse or significant mental illness Patients suffering from depression as measured by a score of >10 on the Patient Health Questionnaire (PHQ9). For clarity, patients diagnosed with depression which is controlled with stable anti-depressive medication and in whom PHQ9 is <10 are eligible to participate in the trial. History of epilepsy, defined as at least two unprovoked seizures occurring greater than 24 hours apart or diagnosis of an epilepsy syndrome, OR a seizure within the last 12 months. Any condition that would prevent the subject from giving voluntary informed consent; An implanted brain stimulator; Any metal in head with the exception of dental work or any ferromagnetic metal -elsewhere in the body; Enrolled or plans to enroll in an interventional trial during this study; Scalp wounds or infections; Claustrophobia precluding MRI; A fixed contraction deformity in the affected limb that would prevent normal dexterity if patient were neurologically intact; Excessive spasticity as indicated by the Modified Ashworth Spasticity (MAS) Scale >2/4 in either elbow flexors, wrist flexors or finger flexors of the affected limb; Previous stroke with residual deficits (TIAs not a reason for exclusion); Premorbid (retrospective) modified Rankin Scale (mRS) score ≥2 of any aetiology; A concurrent progressive neurologic disorder, acute coronary syndrome, severe heart disease (NYHA Classification > 3), or other major medical condition, Confirmed or suspected lower-limb fracture preventing mobilization, patients requiring palliative care Patients planning to undergo any other occupational therapy during the 6 week active treatment period of the trial (see section 5.2 for study schedule) than what is provided in the study A recent injection of botulinium toxin to the affected upper limb in the last 3 months, or the need of an injection of botulinum toxin anytime during the study period and follow up. A recent injection of phenol to the affected upper limb in the last 6 months, or the need of an injection of phenol anytime during the study period and follow up. Ataxia as measured by a score > 1 on item 7 (limb ataxia) of the NIH stroke scale. Severe sensory deficits as measured by a score of 2 on item 8 of the NIH stroke scale. Severe aphasia as measured by a score of > 2 on item 9 (best language) of the NIH stroke scale. Severe neglect as measured by a score of 2 on item 11 (extinction and inattention) of the NIH stroke scale. Patients unable to comprehend or follow verbal commands Based on PI's or local physician's assessment patient unable to tolerate the trial procedure due to medical condition A Mini mental status exam (MMSE) <25.

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 |
| --- | --- |
| Active Comparator: Active<br>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation | Device: Nexstim NBS guided active rTMS<br>* Nexstim NBS guided active rTMS + standardized task-oriented therapy<br>|
| Sham Comparator: Control<br>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation | Device: Nexstim NBS guided sham rTMS<br>* Nexstim NBS guided sham rTMS + standardized task-oriented therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper Extremity Fugl-Meyer Score | Range 0 to 65. HIgher scores indicate better function. Minimal clinically important difference = change of 5 points or more on scale. Outcome measure = proportion of patients in treatment arm gaining at least 5 points on scale between baseline and 6 months after end of treatment. | Change from baseline to 6 months after end of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper Extremity Fugl-Meyer Score | Range 0-65. HIgher scores indicate better function. | Change in score from baseline to 6 months after end of treatment | 
| Arm-Research Action Test (ARAT) | Range 0 to 57. Higher scores indicate better function. | Change in score from baseline to 6 months after end of treatment. | 
| NIH Stroke Scale (NIHSS) | National Institute of Health Stroke Scale - Motor Arm. Range 0 to 4. Lower score indicates better function. | Change in score from baseline to 6 months after end of treatment | 
| Quality of Life Assessment: EQ-5D | EuroQoL - EQ-5D score. Range 0 to 100. HIgher numbers indicate better quality of life. | Change in score from baseline to 6 months after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, rTMS, Motor rehabilitation