Chronic Stroke PatientINSPIRENCT07439367
Multifocal Theta-Burst Stimulation to Enhance Upper Limb Motor Recovery After Stroke (INSPIRE)
A study testing Active iTBS and Tablet-based upper limb training in people with Chronic Stroke Patient and Motor Impairment, run by School of Health Sciences Geneva at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Stroke Patient, Motor Impairment, Neurorehabilitation
- What is being tested?
- Active iTBS and Tablet-based upper limb training
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteSwitzerland
- Study dates
- 5 Sep 2025to 31 Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
- Pregnancy
- Delirium or impaired vigilance
- Inability to participate in one-hour treatment sessions
- Inability to comply with study procedures
- Current or past substance abuse, including excessive alcohol consumption
- Participation in another interventional clinical trial within 30 days prior to enrollment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
University School of Health ▪ HES-SO Genève
Carouge, Canton of Geneva, 1227
Pierre Nicolo, PhD, 0792633543 ext. +41 22 558 64, pierre.nicolo@hesge.ch
About this study
Official title: Advancing Stroke Rehabilitation Through Multifocal Network-based Theta-burst Stimulation and Assistive Technology: Enhancing Upper Limb Motor Learning: A Single-center, Randomized, Sham-controlled Study With Parallel Groups.
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.
Read more
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.
Read the detailed description
Stroke is a leading cause of long-term motor disability, with persistent upper limb impairment affecting a large proportion of individuals in the chronic phase. Despite advances in rehabilitation, recovery of arm function remains limited for many patients. Motor recovery after stroke depends on neuroplastic reorganization within distributed brain networks. While most neuromodulation studies have focused on stimulating the primary motor cortex (M1) alone, growing evidence indicates that motor learning relies on coordinated interactions between multiple cortical regions, particularly the functional connectivity between the parietal cortex (PC) and M1.
Resting-state functional connectivity between parietal and motor areas has been identified as a neurophysiological marker associated with motor performance and recovery potential. Enhancing this network-level connectivity may therefore represent a promising strategy to improve motor learning and functional outcomes after stroke.
The INSPIRE project investigates a novel multifocal intermittent theta-burst stimulation (iTBS) paradigm targeting both M1 and PC. Intermittent theta-burst stimulation is a patterned form of repetitive transcranial magnetic stimulation (rTMS) capable of inducing lasting modulation of cortical excitability. In contrast to conventional monofocal approaches, this study applies neuronavigated iTBS sequentially over M1 and the superior parietal lobule within the affected hemisphere, with the objective of modulating network-level interactions rather than isolated cortical excitability.
The stimulation protocol is combined with structured motor training delivered through a tablet-based interactive device (REAtouch®Lite 2). This system implements a standardized two-dimensional reaching task that allows precise quantification of motor performance and spatio-temporal movement parameters. The combination of neuromodulation and task-specific training is designed to engage Hebbian plasticity mechanisms, whereby stimulation-induced network modulation may facilitate motor learning processes during training.
This study is designed as a single-center, randomized, sham-controlled, triple-blind, parallel-group clinical trial. Thirty-six individuals in the chronic phase after a first stroke (≥6 months) with moderate upper limb impairment will be randomized in a 1:1 ratio to receive either active multifocal iTBS or sham stimulation. Both groups will undergo identical motor training sessions. 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 for behavioral and neurophysiological measures.
The intervention consists of two consecutive days of stimulation combined with motor training. Each session includes neuronavigated iTBS delivered over M1 and PC (600 pulses per target at 70% resting motor threshold), followed by 45 minutes of structured motor training. Sham stimulation reproduces auditory and sensory aspects of active stimulation without inducing a cortical electric field.
Motor performance is assessed using a composite motor performance index derived from reaching accuracy and movement time during a standardized visuo-motor task. Secondary behavioral measures include short-term learning indices, offline consolidation effects, detailed spatio-temporal movement parameters, and clinical motor impairment assessed with the Fugl-Meyer Assessment for Upper Extremity (FMA-UE).
Neurophysiological outcomes include resting-state electroencephalography (EEG) recorded before and after the intervention. Functional connectivity between parietal and motor regions is quantified using frequency-specific coherence measures and graph-theoretical metrics. These analyses aim to determine whether multifocal iTBS enhances cortico-cortical connectivity and whether changes in connectivity are associated with behavioral improvements.
The primary hypothesis is that multifocal iTBS combined with motor training will lead to greater improvements in motor performance compared with sham stimulation. Secondary hypotheses include enhanced short-term motor learning, improved retention of learned motor skills, and increased parieto-motor functional connectivity in the active stimulation group.
This project integrates behavioral, clinical, and neurophysiological measures to evaluate a network-based neuromodulation approach in chronic stroke rehabilitation. By targeting distributed cortical interactions rather than a single cortical region, the study aims to advance precision neurorehabilitation strategies grounded in contemporary models of motor learning and brain network plasticity.
If successful, this intervention paradigm could inform future rehabilitation protocols and support the development of individualized, connectivity-driven therapeutic approaches for stroke recovery.
- Being tested
- Active iTBS, Tablet-based upper limb training, Sham iTBS
- Keywords
- Chronic Stroke, Upper Limb Rehabilitation, Intermittent Theta Burst Stimulation, Tablet-Based Rehabilitation, Neuroplasticity, Motor Learning
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active iTBSDevice
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 trainingDevice
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 iTBSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active iTBS + motor training | Experimental | active iTBS stimulation prior to tablet-based motor training Receives: Device: Active iTBS; Device: Tablet-based upper limb training |
| Sham iTBS + motor training | Sham comparator | sham iTBS stimulation prior to tablet-based motor training Receives: Device: Tablet-based upper limb training; Device: Sham iTBS |
| No iTBS + motor training (healthy controls) | Other | no brain stimulation; tablet-based motor training only Receives: Device: Tablet-based upper limb training |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Day 0) to Day 10
Secondary outcomes (10)
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.
Measured: Baseline (Day 0) to Day 3
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.
Measured: Day 3 to Day 10
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.
Measured: Baseline (Day 0), Day 3, and Day 10
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.
Measured: Baseline (Day 0), Day 3, and Day 10
Change in Mean Movement Speed (cm/s)
Mean movement speed will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.
Movement speed (cm/s) is calculated as the displacement divided by the time between movement initiation (defined as >5 mm displacement from the starting position) and movement stabilization within the target area.
This is a continuous variable with a minimum possible value of 0 cm/s and no predefined upper limit. Higher values indicate faster movement performance.
Changes in mean movement speed over time will be analyzed.
Measured: Baseline (Day 0), Day 3, and Day 10
Change in Mean Movement Smoothness (cm/s³)
Mean movement smoothness will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.
Movement smoothness is quantified using a jerk-based metric (third derivative of position with respect to time), expressed in centimeters per second cubed (cm/s³). The metric reflects the magnitude of trajectory corrections during movement execution.
This is a continuous variable with a minimum possible value of 0 cm/s³ and no predefined upper limit. Lower values indicate smoother movements and better motor control, whereas higher values indicate greater movement irregularity.
Changes in mean movement smoothness over time will be analyzed.
Measured: Baseline (Day 0), Day 3, and Day 10
Change in Mean Maximum Lateral Deviation (cm)
Mean maximum lateral deviation will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.
Maximum lateral deviation (cm) is defined as the greatest perpendicular distance between the participant's actual movement trajectory and the optimal straight-line trajectory from the start position to the target.
This is a continuous variable with a minimum possible value of 0 cm (perfectly straight trajectory) and no predefined upper limit. Lower values indicate better trajectory control and movement accuracy, whereas higher values indicate greater deviation from the optimal path.
Changes in mean maximum lateral deviation over time will be analyzed.
Measured: Baseline (Day 0), Day 3, and Day 10
Change in Mean Directional Error at 100 ms (degrees)
Mean directional error at 100 milliseconds will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.
Directional error (degrees) is defined as the angular deviation between the initial movement direction and the straight-line direction to the target, calculated 100 milliseconds after movement onset. Movement onset is defined as displacement exceeding 5 mm from the starting position.
This is a continuous variable expressed in degrees, with a minimum possible value of 0° (perfect alignment with the target direction) and no predefined upper limit. Lower values indicate greater motor planning accuracy, whereas higher values indicate greater deviation from the intended direction.
Changes in mean directional error over time will be analyzed.
Measured: Baseline (Day 0), Day 3, and Day 10
Change in Mean Reaction Time (seconds)
Mean reaction time will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.
Reaction time (seconds) is defined as the time elapsed between target appearance and movement initiation in the correct direction, defined as an initial movement trajectory within ≤15° of the straight-line direction to the target. Movement initiation is defined as displacement exceeding 5 mm from the starting position.
This is a continuous variable expressed in seconds, with a minimum possible value of 0 seconds and no predefined upper limit. Lower values indicate faster response initiation and better motor preparation, whereas higher values indicate slower response initiation.
Changes in mean reaction time over time will be analyzed.
Measured: Baseline (Day 0), Day 3, and Day 10
Change in Parieto-Motor Functional Connectivity Measured by Resting-State EEG
Resting-state electroencephalography (EEG) will be used to assess functional connectivity between parietal and motor cortical regions.
Functional connectivity will be quantified using frequency-specific coherence values and graph-theoretical network metrics derived from EEG signals. Coherence values range from 0 to 1, with higher values indicating stronger functional connectivity between cortical regions. Graph-based metrics (e.g., global efficiency, clustering coefficient) are continuous measures without fixed theoretical minimum or maximum values; higher values indicate greater network integration or segregation depending on the specific metric analyzed.
Change in these connectivity measures between Baseline (Day 0) and Day 3 will be analyzed to evaluate neurophysiological effects of stimulation.
Measured: Baseline (Day 0) and Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2026
- Study start5 Sep 2025
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Chronic Stroke PatientStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- School of Health Sciences Geneva
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Geneva
- Responsible party
- Principal investigator, Pierre Nicolo, PhD, School of Health Sciences Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07439367
- Sponsor's protocol ID
- 2025-D0020
- Acronym
- INSPIRE
- Status last verified
- Feb 2026
- First submitted
- 16 Feb 2026
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) underlying the results reported in publications will be shared. This includes behavioral motor performance data, spatio-temporal movement parameters, Fugl-Meyer Assessment scores (for stroke participants), resting-state EEG-derived functional connectivity measures, and relevant demographic and clinical variables necessary to reproduce the analyses. All shared datasets will be fully anonymized and stripped of direct and indirect identifiers in accordance with applicable data protection regulations. Data will be made available to qualified researchers upon reasonable request and after approval of a methodologically sound research proposal. A data-sharing agreement will be required to ensure appropriate use of the data.
Publications
Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7(1):13-31.
PubMed 1135616Wanivenhaus F, Espinosa N, Tscholl PM, Krause F, Wirth SH. Quality of Early Union After First Metatarsophalangeal Joint Arthrodesis. J Foot Ankle Surg. 2017 Jan-Feb;56(1):50-53. doi: 10.1053/j.jfas.2016.09.001. Epub 2016 Nov 17.
PubMed 27866887Redolfi N, Lodovichi C. Spontaneous Afferent Activity Carves Olfactory Circuits. Front Cell Neurosci. 2021 Mar 9;15:637536. doi: 10.3389/fncel.2021.637536. eCollection 2021.
PubMed 33767612Kim JW, Choi KH, Yun JH, Jung UW, Kim CS, Choi SH, Cho KS. Bone formation of block and particulated biphasic calcium phosphate lyophilized with Escherichia coli-derived recombinant human bone morphogenetic protein 2 in rat calvarial defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011 Sep;112(3):298-306. doi: 10.1016/j.tripleo.2010.10.025. Epub 2011 Feb 3.
PubMed 21292513El-Hoss J, Sullivan K, Cheng T, Yu NY, Bobyn JD, Peacock L, Mikulec K, Baldock P, Alexander IE, Schindeler A, Little DG. A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells. J Bone Miner Res. 2012 Jan;27(1):68-78. doi: 10.1002/jbmr.528.
PubMed 21956219Van Moerbeke M, Kasim A, Shkedy Z. The Usage of Exon-Exon Splice Junctions for the Detection of Alternative Splicing using the REIDS model. Sci Rep. 2018 May 29;8(1):8331. doi: 10.1038/s41598-018-26695-9.
PubMed 29844567Sobczyk O, Battisti-Charbonney A, Fierstra J, Mandell DM, Poublanc J, Crawley AP, Mikulis DJ, Duffin J, Fisher JA. A conceptual model for CO(2)-induced redistribution of cerebral blood flow with experimental confirmation using BOLD MRI. Neuroimage. 2014 May 15;92:56-68. doi: 10.1016/j.neuroimage.2014.01.051. Epub 2014 Feb 5.
PubMed 24508647Papaleonidopoulos V, Papatheodoropoulos C. beta-adrenergic receptors reduce the threshold for induction and stabilization of LTP and enhance its magnitude via multiple mechanisms in the ventral but not the dorsal hippocampus. Neurobiol Learn Mem. 2018 May;151:71-84. doi: 10.1016/j.nlm.2018.04.010. Epub 2018 Apr 10.
PubMed 29653257Haziza C, de La Bourdonnaye G, Merlet S, Benzimra M, Ancerewicz J, Donelli A, Baker G, Picavet P, Ludicke F. Assessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence: A randomized controlled study in confinement. Regul Toxicol Pharmacol. 2016 Nov;81:489-499. doi: 10.1016/j.yrtph.2016.09.014. Epub 2016 Sep 29.
PubMed 27693654Su X, Sheng H, Huang Y, Li X, Zhang W, Zhao X, Li C, Liu L. Clinical and GAA gene mutation analysis in 21 Chinese patients with classic infantile pompe disease. Eur J Med Genet. 2020 Dec;63(12):103997. doi: 10.1016/j.ejmg.2020.103997. Epub 2020 Jul 22.
PubMed 32711049Venken KJ, Simpson JH, Bellen HJ. Genetic manipulation of genes and cells in the nervous system of the fruit fly. Neuron. 2011 Oct 20;72(2):202-30. doi: 10.1016/j.neuron.2011.09.021.
PubMed 22017985Yorganci K, Krepel C, Weigelt JA, Edmiston CE. Activity of antibacterial impregnated central venous catheters against Klebsiella pneumoniae. Intensive Care Med. 2002 Apr;28(4):438-42. doi: 10.1007/s00134-002-1243-4. Epub 2002 Mar 15.
PubMed 11967598Huber C, Martensson A, Bokoch GM, Nemazee D, Gavin AL. FGD2, a CDC42-specific exchange factor expressed by antigen-presenting cells, localizes to early endosomes and active membrane ruffles. J Biol Chem. 2008 Dec 5;283(49):34002-12. doi: 10.1074/jbc.M803957200. Epub 2008 Oct 6.
PubMed 18838382Kim AH, Lee S, Jeon S, Kim GT, Lee EJ, Kim D, Kim Y, Park TS. Addition of an N-Terminal Poly-Glutamate Fusion Tag Improves Solubility and Production of Recombinant TAT-Cre Recombinase in Escherichia coli. J Microbiol Biotechnol. 2020 Jan 28;30(1):109-117. doi: 10.4014/jmb.1909.09028.
PubMed 31693834Kim SH, Kalinina NO, Andreev I, Ryabov EV, Fitzgerald AG, Taliansky ME, Palukaitis P. The C-terminal 33 amino acids of the cucumber mosaic virus 3a protein affect virus movement, RNA binding and inhibition of infection and translation. J Gen Virol. 2004 Jan;85(Pt 1):221-230. doi: 10.1099/vir.0.19583-0.
PubMed 14718637
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Advancing Stroke Rehabilitation Through Multifocal Network-based Theta-burst Stimulation and Assistive Technology: Enhancing Upper Limb Motor Learning: A Single-center, Randomized, Sham-controlled Study With Parallel Groups.
- ClinicalTrials.gov ID
- NCT07439367
- Acronym / sponsor ID
- INSPIRE / 2025-D0020
- Keywords
- Chronic Stroke, Upper Limb Rehabilitation, Intermittent Theta Burst Stimulation, Tablet-Based Rehabilitation, Neuroplasticity, Motor Learning
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- School of Health Sciences GenevaUniversity, hospital or other
- Collaborators
- University Hospital, Geneva
- Study start
- 5 Sep 2025 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 27 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Stroke is a leading cause of long-term motor disability, with persistent upper limb impairment affecting a large proportion of individuals in the chronic phase. Despite advances in rehabilitation, recovery of arm function remains limited for many patients. Motor recovery after stroke depends on neuroplastic reorganization within distributed brain networks. While most neuromodulation studies have focused on stimulating the primary motor cortex (M1) alone, growing evidence indicates that motor learning relies on coordinated interactions between multiple cortical regions, particularly the functional connectivity between the parietal cortex (PC) and M1.
Resting-state functional connectivity between parietal and motor areas has been identified as a neurophysiological marker associated with motor performance and recovery potential. Enhancing this network-level connectivity may therefore represent a promising strategy to improve motor learning and functional outcomes after stroke.
The INSPIRE project investigates a novel multifocal intermittent theta-burst stimulation (iTBS) paradigm targeting both M1 and PC. Intermittent theta-burst stimulation is a patterned form of repetitive transcranial magnetic stimulation (rTMS) capable of inducing lasting modulation of cortical excitability. In contrast to conventional monofocal approaches, this study applies neuronavigated iTBS sequentially over M1 and the superior parietal lobule within the affected hemisphere, with the objective of modulating network-level interactions rather than isolated cortical excitability.
The stimulation protocol is combined with structured motor training delivered through a tablet-based interactive device (REAtouch®Lite 2). This system implements a standardized two-dimensional reaching task that allows precise quantification of motor performance and spatio-temporal movement parameters. The combination of neuromodulation and task-specific training is designed to engage Hebbian plasticity mechanisms, whereby stimulation-induced network modulation may facilitate motor learning processes during training.
This study is designed as a single-center, randomized, sham-controlled, triple-blind, parallel-group clinical trial. Thirty-six individuals in the chronic phase after a first stroke (≥6 months) with moderate upper limb impairment will be randomized in a 1:1 ratio to receive either active multifocal iTBS or sham stimulation. Both groups will undergo identical motor training sessions. 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 for behavioral and neurophysiological measures.
The intervention consists of two consecutive days of stimulation combined with motor training. Each session includes neuronavigated iTBS delivered over M1 and PC (600 pulses per target at 70% resting motor threshold), followed by 45 minutes of structured motor training. Sham stimulation reproduces auditory and sensory aspects of active stimulation without inducing a cortical electric field.
Motor performance is assessed using a composite motor performance index derived from reaching accuracy and movement time during a standardized visuo-motor task. Secondary behavioral measures include short-term learning indices, offline consolidation effects, detailed spatio-temporal movement parameters, and clinical motor impairment assessed with the Fugl-Meyer Assessment for Upper Extremity (FMA-UE).
Neurophysiological outcomes include resting-state electroencephalography (EEG) recorded before and after the intervention. Functional connectivity between parietal and motor regions is quantified using frequency-specific coherence measures and graph-theoretical metrics. These analyses aim to determine whether multifocal iTBS enhances cortico-cortical connectivity and whether changes in connectivity are associated with behavioral improvements.
The primary hypothesis is that multifocal iTBS combined with motor training will lead to greater improvements in motor performance compared with sham stimulation. Secondary hypotheses include enhanced short-term motor learning, improved retention of learned motor skills, and increased parieto-motor functional connectivity in the active stimulation group.
This project integrates behavioral, clinical, and neurophysiological measures to evaluate a network-based neuromodulation approach in chronic stroke rehabilitation. By targeting distributed cortical interactions rather than a single cortical region, the study aims to advance precision neurorehabilitation strategies grounded in contemporary models of motor learning and brain network plasticity.
If successful, this intervention paradigm could inform future rehabilitation protocols and support the development of individualized, connectivity-driven therapeutic approaches for stroke recovery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Active iTBS + motor training | Experimental | Device: Active iTBS, Device: Tablet-based upper limb trainingactive iTBS stimulation prior to tablet-based motor training |
| Sham iTBS + motor training | Sham comparator | Device: Tablet-based upper limb training, Device: Sham iTBSsham iTBS stimulation prior to tablet-based motor training |
| No iTBS + motor training (healthy controls) | Other | Device: Tablet-based upper limb trainingno brain stimulation; tablet-based motor training only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active iTBSStandard 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. | Device | Active iTBS + motor training |
| Tablet-based upper limb trainingREAtouch® 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. | Device | Active iTBS + motor training, No iTBS + motor training (healthy controls), Sham iTBS + motor training |
| Sham iTBSSham 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. | Device | Sham iTBS + motor training |
Primary outcome
Change in Global Motor Performance Index (Baseline to Day 10)
Time frame: Baseline (Day 0) 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.
10 secondary outcomes
Change in Short-Term Motor Performance Index (Baseline to Day 3)
Time frame: Baseline (Day 0) to Day 3
Offline Motor Consolidation Index (Day 3 to Day 10)
Time frame: Day 3 to Day 10
Change in Upper Limb Motor Impairment (Fugl-Meyer Assessment - Upper Extremity)
Time frame: Baseline (Day 0), Day 3, and Day 10
Change in Mean Number of Reaching Errors
Time frame: Baseline (Day 0), Day 3, and Day 10
Change in Mean Movement Speed (cm/s)
Time frame: Baseline (Day 0), Day 3, and Day 10
Change in Mean Movement Smoothness (cm/s³)
Time frame: Baseline (Day 0), Day 3, and Day 10
Change in Mean Maximum Lateral Deviation (cm)
Time frame: Baseline (Day 0), Day 3, and Day 10
Change in Mean Directional Error at 100 ms (degrees)
Time frame: Baseline (Day 0), Day 3, and Day 10
Change in Mean Reaction Time (seconds)
Time frame: Baseline (Day 0), Day 3, and Day 10
Change in Parieto-Motor Functional Connectivity Measured by Resting-State EEG
Time frame: Baseline (Day 0) and Day 3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Background: PubMed 1135616Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7(1):13-31.
- Background: PubMed 27866887Wanivenhaus F, Espinosa N, Tscholl PM, Krause F, Wirth SH. Quality of Early Union After First Metatarsophalangeal Joint Arthrodesis. J Foot Ankle Surg. 2017 Jan-Feb;56(1):50-53. doi: 10.1053/j.jfas.2016.09.001. Epub 2016 Nov 17.
- Background: PubMed 33767612Redolfi N, Lodovichi C. Spontaneous Afferent Activity Carves Olfactory Circuits. Front Cell Neurosci. 2021 Mar 9;15:637536. doi: 10.3389/fncel.2021.637536. eCollection 2021.
- Background: PubMed 21292513Kim JW, Choi KH, Yun JH, Jung UW, Kim CS, Choi SH, Cho KS. Bone formation of block and particulated biphasic calcium phosphate lyophilized with Escherichia coli-derived recombinant human bone morphogenetic protein 2 in rat calvarial defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011 Sep;112(3):298-306. doi: 10.1016/j.tripleo.2010.10.025. Epub 2011 Feb 3.
- Background: PubMed 21956219El-Hoss J, Sullivan K, Cheng T, Yu NY, Bobyn JD, Peacock L, Mikulec K, Baldock P, Alexander IE, Schindeler A, Little DG. A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells. J Bone Miner Res. 2012 Jan;27(1):68-78. doi: 10.1002/jbmr.528.
- Background: PubMed 29844567Van Moerbeke M, Kasim A, Shkedy Z. The Usage of Exon-Exon Splice Junctions for the Detection of Alternative Splicing using the REIDS model. Sci Rep. 2018 May 29;8(1):8331. doi: 10.1038/s41598-018-26695-9.
- Background: PubMed 24508647Sobczyk O, Battisti-Charbonney A, Fierstra J, Mandell DM, Poublanc J, Crawley AP, Mikulis DJ, Duffin J, Fisher JA. A conceptual model for CO(2)-induced redistribution of cerebral blood flow with experimental confirmation using BOLD MRI. Neuroimage. 2014 May 15;92:56-68. doi: 10.1016/j.neuroimage.2014.01.051. Epub 2014 Feb 5.
- Background: PubMed 29653257Papaleonidopoulos V, Papatheodoropoulos C. beta-adrenergic receptors reduce the threshold for induction and stabilization of LTP and enhance its magnitude via multiple mechanisms in the ventral but not the dorsal hippocampus. Neurobiol Learn Mem. 2018 May;151:71-84. doi: 10.1016/j.nlm.2018.04.010. Epub 2018 Apr 10.
- Background: PubMed 27693654Haziza C, de La Bourdonnaye G, Merlet S, Benzimra M, Ancerewicz J, Donelli A, Baker G, Picavet P, Ludicke F. Assessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence: A randomized controlled study in confinement. Regul Toxicol Pharmacol. 2016 Nov;81:489-499. doi: 10.1016/j.yrtph.2016.09.014. Epub 2016 Sep 29.
- Background: PubMed 32711049Su X, Sheng H, Huang Y, Li X, Zhang W, Zhao X, Li C, Liu L. Clinical and GAA gene mutation analysis in 21 Chinese patients with classic infantile pompe disease. Eur J Med Genet. 2020 Dec;63(12):103997. doi: 10.1016/j.ejmg.2020.103997. Epub 2020 Jul 22.
- Background: PubMed 22017985Venken KJ, Simpson JH, Bellen HJ. Genetic manipulation of genes and cells in the nervous system of the fruit fly. Neuron. 2011 Oct 20;72(2):202-30. doi: 10.1016/j.neuron.2011.09.021.
- Background: PubMed 11967598Yorganci K, Krepel C, Weigelt JA, Edmiston CE. Activity of antibacterial impregnated central venous catheters against Klebsiella pneumoniae. Intensive Care Med. 2002 Apr;28(4):438-42. doi: 10.1007/s00134-002-1243-4. Epub 2002 Mar 15.
- Advancing Upper Limb Stroke Rehab \& Assistive TechnologyLink provided by the sponsor.
- Advancing Upper Limb Stroke Rehab \& Assistive TechnologyLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) underlying the results reported in publications will be shared. This includes behavioral motor performance data, spatio-temporal movement parameters, Fugl-Meyer Assessment scores (for stroke participants), resting-state EEG-derived functional connectivity measures, and relevant demographic and clinical variables necessary to reproduce the analyses. All shared datasets will be fully anonymized and stripped of direct and indirect identifiers in accordance with applicable data protection regulations. Data will be made available to qualified researchers upon reasonable request and after approval of a methodologically sound research proposal. A data-sharing agreement will be required to ensure appropriate use of the data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active iTBS and Tablet-based upper limb training in people with Chronic Stroke Patient and Motor Impairment, run by School of Health Sciences Geneva at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pierre Nicolo, PhD (+41792633543 ext. +41 22 558 64, pierre.nicolo@hesge.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Global Motor Performance Index (Baseline to Day 10) (time frame: Baseline (Day 0) to Day 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07439367, which also lists 28 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.