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

NCT07439367 | Recruiting

• 1 other identifier: 2025-D0020
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Stroke Patient; Motor Impairment; Neurorehabilitation; Theta Burst Stimulation

Keywords

Chronic Stroke; Upper Limb Rehabilitation; Intermittent Theta Burst Stimulation; Tablet-Based Rehabilitation; Neuroplasticity; Motor Learning

Outcome Measures

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.

  Baseline (Day 0) to Day 10

Secondary Outcomes (10)

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

  Baseline (Day 0) to Day 3

• Offline Motor Consolidation Index (Day 3 to Day 10)

  Day 3 to Day 10

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

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

• Change in Mean Number of Reaching Errors

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

• Change in Mean Movement Speed (cm/s)

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

Other Outcomes (3)

• Upper Limb Active Duration (minutes)

  During Intervention Sessions (Day 1 and Day 2)

• Mean Movement Intensity (vector magnitude counts)

  During Intervention Sessions (Day 1 and Day 2)

• Percentage of Active Time (%)

  During Intervention Sessions (Day 1 and Day 2)

Study Arms (3)

Active iTBS + motor training

EXPERIMENTAL

active iTBS stimulation prior to tablet-based motor training

Device: Active iTBS; Device: Tablet-based upper limb training

Sham iTBS + motor training

SHAM COMPARATOR

sham iTBS stimulation prior to tablet-based motor training

Device: Tablet-based upper limb training; Device: Sham iTBS

No iTBS + motor training (healthy controls)

OTHER

no brain stimulation; tablet-based motor training only

Device: Tablet-based upper limb training

Interventions

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.

Active iTBS + motor training

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.

Active iTBS + motor training; No iTBS + motor training (healthy controls); Sham iTBS + motor training

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.

Sham iTBS + motor training

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For Stroke Participants:
• Age ≥ 18 years
• First-ever ischemic or hemorrhagic stroke
• Time since stroke ≥ 6 months
• Unilateral upper limb hemiparesis
• Fugl-Meyer Assessment Upper Extremity (FMA-UE) score between 29 and 57
• Modified Ashworth Scale score \< 2 at elbow, wrist, or finger flexors
• Manual muscle testing ≥ 3/5 in proximal upper limb muscles (deltoid, biceps, triceps, wrist pronators/supinators)
• Ability to understand and follow study procedures
• Provided written informed consent
• For Healthy Participants:
• Age ≥ 18 years
• No history of neurological disease
• Ability to understand and follow study procedures
• Provided written informed consent

You may not qualify if:

• For Stroke Participants:
• 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
• Implanted electronic or metallic devices (e.g., pacemaker, neurostimulator) incompatible with TMS
• Severe comorbid conditions affecting the upper limb (traumatic, rheumatologic, osteoarticular, or neurodegenerative disorders)
• Pregnancy
• Delirium or impaired vigilance
• Inability to participate in one-hour treatment sessions
• Inability to comply with study procedures (e.g., language barrier, psychological disorder, dementia)
• Current or past substance abuse, including excessive alcohol consumption
• Participation in another interventional clinical trial within 30 days prior to enrollment
• For Healthy Participants:
• Severe musculoskeletal or neurological condition affecting the non-dominant upper limb

Sponsors & Collaborators

• School of Health Sciences Geneva: lead
• University Hospital, Geneva: collaborator

Study Sites (1)

University School of Health ▪ HES-SO Genève

Carouge, Canton of Geneva, 1227, Switzerland

RECRUITING

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Related Links

• Advancing Upper Limb Stroke Rehab \& Assistive Technology
• Advancing Upper Limb Stroke Rehab \& Assistive Technology

Central Study Contacts

Pierre Nicolo, PhD

CONTACT

+41792633543; pierre.nicolo@hesge.ch

Nicolas Nicastro, MD

CONTACT

+41 22 372 36 24; nicolas.nicastro@hug.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is conducted using a triple-blind design. Participants, outcome assessors, and therapists administering the stimulation and motor training are blinded to group allocation. Active and sham stimulation procedures are identical in appearance, sound, and setup. A placebo coil is used in the sham condition to replicate sensory and auditory aspects of active stimulation without generating a cortical electric field. Group allocation is managed by an independent investigator not involved in intervention delivery, outcome assessment, or data analysis. The randomization list is securely stored and inaccessible to blinded study personnel.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a single-center, randomized, sham-controlled, triple-blind, parallel-group clinical trial. Thirty-six patients with chronic stroke-related upper limb motor impairment will be randomly assigned in a 1:1 ratio to receive either active multifocal intermittent theta-burst stimulation (iTBS) or sham stimulation. Both groups will undergo identical structured motor training using an interactive tablet-based device. In addition, a group of ten age- and sex-matched healthy participants will complete the same motor training protocol without brain stimulation to provide normative reference data. Behavioral and neurophysiological outcomes will be assessed longitudinally at baseline, post-intervention, and follow-up.

Study Record Dates

• First Submitted: February 16, 2026
• First Posted: February 27, 2026
• Study Start: September 5, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Individual participant data (IPD) and supporting information will be available beginning 6 months after publication of the primary results and will remain available for a period of 5 years following publication.
• Access Criteria: De-identified individual participant data (IPD) and supporting documents (study protocol, statistical analysis plan, and analytic code) will be available to qualified researchers whose proposed use of the data has been approved by the study investigators. Access will be granted upon submission of a methodologically sound research proposal that is aligned with the scientific objectives of the original study. Requests must include a research plan, statistical analysis outline, and evidence of institutional affiliation. Data will be shared under a formal data-sharing agreement to ensure appropriate use, confidentiality, and compliance with applicable data protection regulations. Data will be transferred securely via encrypted electronic files or through a controlled-access institutional data repository.

Locations

CH (1)