Health TrialsbyHealthPanel

Multifocal Theta-Burst Stimulation to Enhance Upper Limb Motor Recovery After Stroke (INSPIRE)

ConditionsChronic Stroke PatientMotor ImpairmentNeurorehabilitationTheta Burst Stimulation
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorSchool of Health Sciences Geneva

About this trial

Stroke is one of the leading causes of long-term disability worldwide. Many individuals who survive a stroke continue to experience weakness and reduced control of one arm, even months or years after the event. These motor impairments significantly affect independence, daily activities, and quality of life. Despite rehabilitation efforts, recovery of upper limb function remains incomplete for many patients.

Motor recovery after stroke depends on the brain's ability to reorganize itself, a process known as neuroplasticity. Recent research suggests that motor learning and brain recovery are influenced not only by activity in the primary motor cortex (M1), but also by its functional connectivity with other brain regions, particularly the parietal cortex (PC). Strengthening communication between these regions may enhance motor recovery.

This study aims to investigate a novel, non-invasive brain stimulation approach called intermittent theta-burst stimulation (iTBS). Unlike traditional stimulation methods that target a single brain region, this study uses a multifocal stimulation protocol targeting both the primary motor cortex and the parietal cortex. The stimulation is combined with structured motor training using an interactive tablet-based rehabilitation device (REAtouch®Lite 2), designed to improve arm movement through goal-directed reaching tasks.

The study is a single-center, randomized, sham-controlled, triple-blind clinical trial with parallel groups. Thirty-six individuals with chronic stroke-related upper limb impairment will be randomly assigned to receive either active multifocal iTBS or sham (placebo) stimulation. Both groups will complete identical motor training sessions. In addition, ten healthy participants will complete the same motor training protocol (without brain stimulation) to provide reference data.

Participants will attend six visits over approximately 10 days. Assessments will include motor performance tests using the interactive tablet, a standardized clinical motor scale (Fugl-Meyer Assessment for Upper Extremity), and resting-state electroencephalography (EEG) to measure brain connectivity changes.

The primary outcome is improvement in motor performance between baseline and one week after the intervention. Secondary outcomes include short-term motor improvements, retention of learning, changes in movement quality, and changes in brain functional connectivity.

This study seeks to determine whether combining multifocal brain stimulation with targeted motor training can enhance motor learning and promote better recovery of arm function after stroke. If effective, this approach could contribute to the development of more precise, network-based neurorehabilitation strategies.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Age ≥ 18 years

First-ever ischemic or hemorrhagic stroke

Time since stroke ≥ 6 months

Unilateral upper limb hemiparesis

Disqualifiers

Second stroke occurring during the study period

Botulinum toxin injection within 3 months prior to study start

History of one or more epileptic seizures

Metallic object near the stimulation site

Trial design

Design model

Parallel

Treatments tested in this trial

  • Active iTBS

    Device

    Standard 600-pulse intermittent theta burst stimulation (iTBS) can increase corticomotor excitability. The iTBS will be delivered with an intensity of 70% of the individual resting motor threshold (RMT) over the ipsilesional primary motor cortex (M1) and superior parietal lobule using a Magstim Rapid2 stimulator equipped with a figure-of-eight coil. Stimulation will follow the standard iTBS pattern consisting of bursts of 3 pulses at 50 Hz repeated at 5 Hz.

  • Tablet-based upper limb training

    Device

    REAtouch® Lite 2 interactive rehabilitation device will be used for upper limb motor training. REAtouch® Lite 2 is a touchscreen-based, task-oriented rehabilitation device designed to train upper limb movements through interactive exercises. The device targets (1) goal-directed reaching movements, (2) hand transport toward visual targets, (3) grasp and release coordination in a two-dimensional workspace, and (4) movement accuracy and speed. Training is supported by customizable visual feedback and task-specific interactive exercises integrated into the device.

  • Sham iTBS

    Device

    Sham intermittent theta burst stimulation (iTBS) mimics the auditory and somatosensory characteristics of active stimulation without inducing a biologically effective cortical electric field. Sham stimulation will be delivered over the ipsilesional primary motor cortex (M1) and superior parietal lobule using a placebo coil identical in appearance, sound, and positioning to the active coil. Stimulation procedures, session duration, neuronavigation, and device setup are identical to the active iTBS condition to ensure participant and assessor blinding.

Treatment groups

46 Participants
are divided into 3 treatment groups
Group A: Active iTBS + motor trainingExperimental treatment 2 interventions
Group B: Sham iTBS + motor trainingSham comparator 2 interventions
Group C: No iTBS + motor training (healthy controls)Other 1 intervention

Trial outcomes

Primary outcomes

1

Change in Global Motor Performance Index (Baseline to Day 10)

The primary outcome is the change in the Global Motor Performance Index score between baseline (Day 0) and post-intervention follow-up (Day 10). The Global Motor Performance Index is a composite performance score derived from a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device. The index integrates movement accuracy (number of errors) and movement time into a single continuous score. The score ranges from -100 to +100, with lower (more negative) values indicating better motor performance and improvement over time, and higher values indicating worse performance.

Time frame
Baseline (Day 0) to Day 10

Secondary outcomes

1

Change in Short-Term Motor Performance Index (Baseline to Day 3)

This outcome evaluates short-term motor learning effects by measuring the change in the Short-Term Motor Performance Index score between Baseline (Day 0) and immediate post-intervention (Day 3). The Short-Term Motor Performance Index is a composite continuous score derived from a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device. The index integrates movement accuracy (number of errors) and movement time into a single performance metric. The score ranges from -100 (best motor performance) to +100 (worst motor performance). Lower (more negative) scores indicate better motor performance, and a decrease in the score over time reflects motor improvement.

Time frame
Baseline (Day 0) to Day 3
2

Offline Motor Consolidation Index (Day 3 to Day 10)

This outcome assesses motor memory consolidation by measuring the change in the Offline Motor Consolidation Index score between immediate post-intervention (Day 3) and follow-up (Day 10). The Offline Motor Consolidation Index is a continuous composite score derived from the same standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device. The index reflects performance retention or change after completion of the stimulation and training sessions. The score ranges from -100 (best motor performance) to +100 (worst motor performance). Lower (more negative) scores indicate better motor performance. A decrease in the score between Day 3 and Day 10 reflects performance improvement, whereas stable scores indicate retention and an increase indicates performance deterioration.

Time frame
Day 3 to Day 10
3

Change in Upper Limb Motor Impairment (Fugl-Meyer Assessment - Upper Extremity)

Upper limb motor impairment will be assessed using the Fugl-Meyer Assessment - Upper Extremity (FMA-UE), a validated clinical scale measuring motor function of the upper limb after stroke. The FMA-UE total score ranges from 0 to 66, where 0 indicates severe motor impairment and 66 indicates normal motor function. Higher scores represent better motor function. Change in FMA-UE scores over time will be analyzed to evaluate clinical motor recovery.

Time frame
Baseline (Day 0), Day 3, and Day 10
4

Change in Mean Number of Reaching Errors

The mean number of reaching errors will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device. An error is defined as failure to reach or stabilize within the predefined target area during a trial. The outcome is a continuous variable representing the average number of errors per session. The minimum possible value is 0 (no errors), with no predefined upper limit. Higher values indicate worse motor performance. Changes in the mean number of errors over time will be analyzed.

Time frame
Baseline (Day 0), Day 3, and Day 10

Other outcomes

1

Upper Limb Active Duration (minutes)

Upper limb activity during motor training sessions will be quantified using a wrist-worn ActiGraph® device. Active duration (minutes) is defined as the total time during each training session in which wrist acceleration exceeds the predefined activity threshold. This is a continuous variable expressed in minutes, with a minimum possible value of 0 minutes and a maximum corresponding to the total session duration. Higher values indicate greater active training time. These values will be used to verify equivalence of training dose across study groups.

Time frame
During Intervention Sessions (Day 1 and Day 2)
2

Mean Movement Intensity (vector magnitude counts)

Upper limb movement intensity during motor training sessions will be quantified using a wrist-worn ActiGraph® device. Mean movement intensity is calculated as the average vector magnitude of triaxial acceleration signals recorded during each training session. This is a continuous variable expressed in activity counts (vector magnitude units) with no predefined theoretical maximum. Higher values indicate greater movement intensity. These values will be used to verify equivalence of training intensity across study groups.

Time frame
During Intervention Sessions (Day 1 and Day 2)
3

Percentage of Active Time (%)

Upper limb activity during motor training sessions will be quantified using a wrist-worn ActiGraph® device. Percentage of active time (%) is defined as the proportion of total session time during which wrist acceleration exceeds the predefined activity threshold. This is a continuous variable expressed as a percentage ranging from 0% to 100%. Higher values indicate greater proportion of active training time. These values will be used to verify equivalence of training exposure across study groups.

Time frame
During Intervention Sessions (Day 1 and Day 2)

Sponsors and contacts

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School of Health Sciences Geneva

Lead sponsor

University Hospital, Geneva

Collaborator

Source ClinicalTrials.gov
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