Efficacy and Safety of rTMS Plus Rehabilitation for the Improvement of the Upper Extremity in Stroke (ERES)

Study Overview
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Brief Summary
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The rehabilitation of the upper limb after a stroke is a challenge due to its complexity and the important cerebral representation of it, particularly of the hand. Repetitive transcranial magnetic stimulation (rTMS) is a tool that can broaden the effect of rehabilitation and thus appears to be observed in different studies performed in patients in chronic phase. However, there are little data on its usefulness before 6 months after the stroke. The variability in the presentation, the fact that it is a phase where the motor deficit of the upper limb coexists with other deficits and medical problems partly explain the lack of specific studies. The investigators present here a preliminary study on the efficacy of rTMS associated with the rehabilitation program of the paretic upper extremity due to a stroke in comparison with sham rTMS. Patients (with moderate to mild involvement) will be randomly distributed in the two study groups and will be evaluated both clinically and neurophysiologically before and after the sessions to try to demonstrate if there is a positive effect in a safe manner.

Official Title
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Pilot Study to Evaluate the Efficacy and Safety of rTMS Associated With Rehabilitation for the Improvement of the Functionality of the Upper Extremity in Stroke

Conditions
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Stroke, Arm Paralysis

Intervention / Treatment
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* Device: Real rTMS (Magstim)
* Device: Sham rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a stroke (ischemic-hemorrhagic) that conditions a limitation unilateral (brachial monoparesis or hemiparesis) and presenting a moderate or mild deficit (motor score on the FM scale ≥ 22 at the motor level of the upper extremity) To participate in the study the patient must sign an informed consent and be older than 18 y.o. Exclusion Criteria: Patients with epilepsy or those with devices will be excluded from the study in your body or metallic at the brain level, as well as patients with craniotomy without cranioplasty. Also excluded are all patients whose conditions prevent them from complying with the rehabilitation protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: It is a randomized design (rTMS vs simulated stimulation before upper limb rehabilitation session) in patients with a single stroke (< 6 months) and unilateral involvement with upper limb paresis (Fugl Meyer > 22).Patients received 15 consecutive rTMS (real or not) plus rehabilitation. Clinical evaluation will be performed before, at the end and one month after the intervention. A neurophysiological exam will be performed before and after the intervention also.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Real rTMS<br>rTMS (Magstim Super Rapid, Magstim Company, Whitland, Wales, UK) with eight-shaped coil (1 Hz, 1500 stimuli) in M1of the contralateral hemisphere to the lesion (healthy side). M1 is defined like the hot spot to elucidated a motor evoked potential in the Abductor Pollicis Brevis (APB) muscle of the contralateral hand. Intervention will be performed before one hour rehabilitation session of the upper limb according to our clinical protocol, completing 15 sessions. | Device: Real rTMS (Magstim)<br>* See arm description<br>|
| Sham Comparator: Sham rTMS<br>Sham rTMS (Magstim Super Rapid, Magstim Company, Whitland, Wales, UK) with eight-shaped coil (1 Hz, 1500 stimuli) in M1of the contralateral hemisphere to the lesion (healthy side). Investigators will make the simulation disconnecting the coil but keeping its position during the same time as the real one. Intervention will be performed before one hour rehabilitation session of the upper limb according to our clinical protocol, completing 15 sessions. | Device: Sham rTMS<br>* See arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in functionality of the upper limb measured in Fugl-Meyer (F-M) scale | Changes in the measure in F-M scale (numeric, *arm strength subscale*): FUGL-MEYER ASSESSMENT UPPER EXTREMITY (FMA-UE) (Fugl-Meyer et al., Scand J Rehabil Med 1975), using the motor function subscore (0 to 66, more functionality with high score) | Before (during 7 days before the 1st stimulation day); at the end (during 7 days after the 15th stimulation day); one month after the last stimulation (limits 7 days before or after the exact data) | 
| Change in functionality of the upper limb measured in Block test | Changes in the measure in Box and Block test (numeric, *total scale*) BOX AND BLOCKS TEST (Mathiowetz et al, Am J Occup Ther 1985) The score is the number of blocks carried from one compartment to the other in one minute. Score each hand separately. Maximum 150 blocks | Before (during 7 days before the 1st stimulation day); at the end (during 7 days after the 15th stimulation day); one month after the last stimulation (limits 7 days before or after the exact data) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in functionality of the upper limb measured in Action Research Arm Test (ARAT) | Changes in the measure in ARAT (numeric, *total scale*) ACTION RESEARCH ARM TEST (Lyle RC, Int J Rehabil Res 1981) Score from 0 to 57 (better function with high score) | Before (during 7 days before the 1st stimulation day); at the end (during 7 days after the 15th stimulation day); one month after the last stimulation (limits 7 days before or after the exact data) | 
| Changes in functionality of the upper limb measured in 9-Hole Peg Test (9-HPT) | Changes in the measure in 9-HPT (time, seconds *total scale*) NINE HOLE PEG TEST (Mathiowetz et al, Occup Therap J Resaerach 1985) Time in second to perform the whole test will be recordered (better with less time) | Before (during 7 days before the 1st stimulation day); at the end (during 7 days after the 15th stimulation day); one month after the last stimulation (limits 7 days before or after the exact data) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, upper limb rehabilitation, rTMS