Theta-Burst-Stimulation in Recurrent Stroke Recovery

Study Overview
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Brief Summary
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The present study aims at investigating the effects of intermittent theta-burst stimulation (iTBS) for motor recovery in recurrent stroke patients. Therefore a daily intervention of repetitive transcranial magnetic stimulation over 8 days combined with subsequent physiotherapy is compared to a control condition, sham stimulation combined with subsequent physiotherapy. Motor function, degree of disability and quality of life are examined in order to evaluate the effects of iTBS in the rehabilitation of recurrent stroke patients in the first weeks and after three months.

Detailed Description
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To date, the majority of neuromodulation approaches aiming at improving motor recovery after stroke are limited to patients with first-ever ischemic stroke. Therefore, rehabilitation of recurrent stroke mainly includes physiotherapy and occupational therapy. Yet, particular these patients retain movement impairment relevant for activities of daily living. By using repetitive transcranial magnetic stimulation (rTMS), it is possible to promote recovery of connectivity between brain regions, particularly after stroke and thereby improve motor performance. Previous data indicate that intermittent theta-burst stimulation (iTBS), a protocol of neuromodulation, enhances the effects of subsequent motor training in early rehabilitation after stroke. The current study aims at investigating whether daily repetitive transcranial magnetic stimulation over 8 days combined with subsequent physiotherapy leads to better motor recovery in recurrent stroke, compared to control condition, physiotherapy after sham stimulation. Motor function, degree of disability and quality of life are examined in order to evaluate the effects of iTBS in the rehabilitation of recurrent stroke patients in the first weeks and after three months.

Official Title
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Theta-Burst-Stimulation in Recurrent Stroke Recovery

Conditions
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Stroke, Neurorehabilitation

Intervention / Treatment
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* Device: Magstim Super Rapid2 System
* Device: Magstim Super Rapid2 System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written consent age: 40-90 years recurrent stroke hemiparesis with impaired hand motor function Exclusion Criteria: Subjects who are legally detained in an official institute (§20 MPG) Electronic implants or ferromagnetic Implants located in the head, neck or thorax (e.g. clips, intracranial shunt, artificial heart valve, pacemaker) Medication pump (e.g. insulin pump) Metal splinters in eye or head Pregnancy / breastfeeding Severe Neurodegenerative disease Severe Neuroinflammatory disease History of seizures / epilepsy Physical addiction to alcohol, medication, or drugs (excluded: nicotine) Insufficient compliance Present or past malignant tumor involving the central nervous system Severe Psychiatric disease Frequent medication with benzodiazepines, high-potency antipsychotics or tricyclic antidepressants before hospitalization or long-term during hospitalization

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Real-iTBS<br> | Device: Magstim Super Rapid2 System<br>* Intermittent theta-burst-stimulation (iTBS) protocol<br>|
| Sham Comparator: Sham-iTBS<br> | Device: Magstim Super Rapid2 System<br>* Sham stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative grip force | grip force as measured with vigorimeter | 3 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative grip force | Grip force as measured with vigorimeter | After 8 days of intervention, and 3 months of enrollment | 
| Motor function | Action Research Arm Test, ARAT | After 8 days of intervention, and 3 months of enrollment | 
| Motor function | Fugl-Meyer Motor Scale of the upper extremity, FM The Fugl-Meyer Assessment scale is an ordinal scale that has 3 points for each item. A zero score is given for the item if the subject cannot do the task. A score of 1 is given when the task is performed partially and a score of 2 is given when the task is performed fully. Minimum score in upper limb = 0 Maximum score in upper limb = 66, Subscales are summed | After 8 days of intervention, and 3 months of enrollment | 
| Stroke severity | National Instituts of Health Stroke Scale, NIHSS The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. | After 8 days of intervention, and 3 months of enrollment | 
| Degree of disability | Modified Rankin Scale, mRS The scale runs from 0-6, running from perfect health (0) without symptoms to death (6). | After 8 days of intervention, and 3 months of enrollment | 
| Motor cortex excitability/ Motor evoked potential | Motor evoked potential (MEP) induced by stimulation of the affected motor cortex | After 8 days of intervention, and 3 months of enrollment | 
| Motor cortex excitability/ Resting motor threshold | Resting motor threshold as measured by stimulation of the affected motor cortex, RMT | After 8 days of intervention, and 3 months of enrollment | 
| Motor cortex excitability/ Short-interval intracortical inhibition | Short-interval intracortical inhibition Short-interval intracortical inhibition (SICI) is a widely used paired-pulse transcranial magnetic stimulation (TMS) measure to assess inhibition in human motor cortex | After 8 days of intervention, and 3 months of enrollment | 
| Motor cortex excitability/ Ipsilateral silent period | Ipsilateral silent period The ipsilateral silent period (iSP) is supposed to be a specific marker of transcallosal motor inhibition. Measured by a short attenuation or interruption of ongoing voluntary electromyographic (EMG) activity in hand muscles induced by focal TMS of the ipsilateral M1. | After 8 days of intervention, and 3 months of enrollment | 
| Quality of life | EuroQol 5D questionnaire, EQ-5D | After 8 days of intervention, and 3 months of enrollment | 
| Activities of daily living at admission and discharge in external rehabilitation facility | Barthel-Index (BI) scores as documented by external rehabilitation facility The Barthel scale is an ordinal scale used to measure performance in activities of daily living (ADL). A higher number is associated with a greater likelihood of being able to live at home with a degree of independence following discharge from hospital. The scale yield a score of 0-100. | After 8 days of intervention, and 3 months of enrollment | 
| Days of rehabilitation after intervention phase | Days of rehabilitation after intervention phase as documented by external rehabilitation facility | 3 months after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent stroke, Stroke, Transcranial Magnetic Stimulation, Theta-Burst-Stimulation