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

Sponsor

Institut Guttmann (Other)

Overall Status

Unknown status

CT.gov ID

NCT04124172

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke Arm Paralysis	Device: Real rTMS (Magstim) Device: Sham rTMS	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Investigator, Outcomes Assessor)

Masking Description:

Participants received rTMS vs simulated stimulation without information of their status. Physical therapy and clinical evaluation will be carried out blindly with respect to the status of brain stimulation. Only the researcher who performs the rTMS knows the intervention condition.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 15, 2019

Anticipated Primary Completion Date :

Dec 15, 2020

Anticipated Study Completion Date :

Apr 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Real rTMS 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) See arm description
Sham Comparator: Sham rTMS 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 See arm description

Arm

Intervention/Treatment

Active Comparator: Real rTMS

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)

See arm description

Sham Comparator: Sham rTMS

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

See arm description

Outcome Measures

Primary Outcome Measures

Change in functionality of the upper limb measured in Fugl-Meyer (F-M) scale [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 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)
Change in functionality of the upper limb measured in Block test [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 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

Secondary Outcome Measures

Changes in functionality of the upper limb measured in Action Research Arm Test (ARAT) [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 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)
Changes in functionality of the upper limb measured in 9-Hole Peg Test (9-HPT) [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 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)

Other Outcome Measures

Neurophysiological exam of cortical excitability: motor threshold collected in the first interoseus dorsal (FID) muscle in the both hands. [Before (during 7 days before the 1st stimulation day); at the end (during 7 days after the 15th stimulation day);]
Motor threshold, mesured in percentage (%): Defined as the minimum stimulation intensity that can produce a motor output (MEP). Fifty microvolts (microV) MEP in 5 of 10 stimulus will be considered. The investigators will use a TMS sitimulation with a focal coil above the scalp in both sides
Neurophysiological exam of cortical excitability: mesure MEPs average in the FID of 10 stimulus in the hot spot of bothsides at 120% of the threshold intensity. [Before (during 7 days before the 1st stimulation day); at the end (during 7 days after the 15th stimulation day);]
MEP will be mesured in microV. The investigators will use a TMS sitimulation with a focal coil above the scalp in both sides.
Neurophysiological exam of cortical excitability:mesure MEPs average after pair pulses in the FID of 10 stimulus in the hot spot of bothsides at 120% of the threshold intensity, preceded of infratreshold stimulus (80%)in 2, 6 and 10 milliseconds [Before (during 7 days before the 1st stimulation day); at the end (during 7 days after the 15th stimulation day);]
Collected the MEP average in the FID of 10 stimulus in the hot spot of bothsides at 120% of the threshold intensity, preceded of infratreshold stimulus (80%)in 2, 6 and 10 milliseconds to study short interval intracortical inhibition (SICI) and short interval intracortical facilitation (SICF). The investigators will use a TMS sitimulation with a focal coil above the scalp in both sides.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.