NCT06116942

Magnetic Brain Stimulation and Computer-based Motor Training for Rehabilitation After Stroke

Repetitive Transcranial Magnetic Stimulation for Enhancing Brain Computer Interphase-induced Plasticity in Stroke: a Crossover Design

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Max Planck Institute for Human Cognitive and Brain Sciences · Academic / Other
• Sex: All
• Age: 20 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The goal of the present clinical trial is to explore whether an innovative technology-based approach can help individuals who have had a stroke and can no longer move their hands with ease. Our approach consists of a combination of two technologies: Transcranial Magnetic Stimulation (TMS) and a Brain-Computer Interface (BCI). The former entails the application of magnetic fields over the head to stimulate the brain preparing it for a better ability to produce movement. The latter consists of measuring brain activity to personalize a type of computer-based training that is designed to increase communication between the brain and the muscles.

Detailed description

Aims of the study: 1. to provide preliminary evidence of the effect of rTMS (repetitive Transcranial Magnetic Stimulation) on brain-computer interface (BCI)-mediated plasticity on individuals with hemiparesis after stroke 2. Measure adherence and withdrawal rates of the present protocol for informing a future large-scale randomized controlled trial The active stimulation (rTMS) consists of an intermittent theta burst (iTBS) protocol whereas the placebo condition encompasses rTMS stimulation delivered with a Sham coil (Sham). Procedures: The study will entail 25 sessions. The study is composed of six different types of sessions in a crossover design: 1. Screening session (day 1): Includes the informed consent form signature, enrollment and BCI calibration 2. Before-treatment and after-treatment sessions (day 2, 13, 14 and 25) include the recording of EEG and MRI data, as well as the application of tests and questionnaires for evaluation of motor function 3. Daily visit with blood draw sessions (days 3, 12, 15 and 24): consist of the delivery of active or sham rTMS followed by BCI training preceded and followed by a blood draw. 4. Daily visit sessions without a blood draw (days 4 to 11 and 16 to 23): consist of the delivery of active or sham rTMS followed by BCI training. After a screening session (day 1), the clinical study begins. The period I of the study begins with a before-treatment session (day 2). Then, the intervention (rTMS or sham followed by BCI training) is delivered during 10 daily visits over a 2-week period excluding weekends (days 3 to 12). Within the daily visits, there are 2 daily visits with blood draws (days 3 and 12) and the rest do not include any blood draws (days 4 to 11). Then, an after-treatment session takes place (day 13). After period I, a washout period of 4 weeks takes place. No measurements or training are required during this time. In Period II of the study, the session flow is repeated except for the screening session. Therefore, period II includes a before-treatment session (day 14), 10 daily visits (days 15 to 24), with 2 daily visits that include blood draws (days 15 and 24), and an after-treatment session (day 25). Research questions: 1. Does rTMS promote better motor recovery after BCI training in comparison to sham? 2. Can rTMS propitiate stronger effects on neural physiology after BCI training in comparison with sham? 3. Is there an association between behavioral and physiological changes after the proposed intervention? 4. What is the adherence and withdrawal rate and reason for withdrawal of the proposed study design and procedures? 5. Is there an association between brain structures associated with motor function at baseline and the changes observed after rTMS? 6. Can applying rTMS have a better effect on self-perceived motor performance in daily activities in comparison to Sham? 7. Are serum molecular markers of plasticity and neural turnover modulated by rTMS? Hypotheses: 1. A higher increase in motor performance will be observed after the rTMS-BCI in comparison with sham-BCI. The motor performance will be assessed as Fugl-Meyer Assessment for upper extremity score as the primary outcome measure; and as the Jebsen Taylor hand function test and BCI accuracy as the secondary outcome measures 2. Higher physiological changes will be observed after rTMS-BCI in comparison with sham-BCI. The electrophysiological changes will be assessed as Motor evoked potentials, as primary outcome measured; and as motor-related cortical potentials, Event-Related Desynchronization and functionalMagnetic Resonance Imaging changes as secondary outcome measures 3. Behavioral and physiological changes will be associated 4. Changes in structural MRI will be associated with behavioral outcome measures after rTMS-BCI and sham-BCI. Structural MRI will be assessed as Fractional Anisotropy changes, as a primary outcome measure; and voxel-based morphometry as a secondary outcome measure 5. Individuals will have a higher perceived improvement in activities of daily living, measured as higher scores in the Upper extremity motor activity log (UE-MAL) and the first and last items of the Stroke impact scale (SIS) questionnaire after rTMS-BCI in comparison with sham-BCI 6. The increase in Brain-Derived Neurotrophic Factor (BDNF) will be higher after rTMS-BCI in comparison with after sham-BCI and an association between BDNF levels and behavioral markers of motor recovery will exist As an exploratory analysis, the investigators will inspect preliminary evidence of the effects of the stimulation by verifying changes in serological markers of neuronal plasticity and turnover.

Conditions

• Chronic Stroke

Interventions

Type	Name	Description
DEVICE	Active rTMS	The Transcranial Magnetic Stimulation will consist of placing a figure-of-eight shape coil of wire over the head of the participants. Then, a brief electric current will pass through the coil, inducing a magnetic field capable of stimulating neurons located beneath the coil. For the active coil, the maximal stimulation intensity is reached beneath the center of the coil. In the present study, the intermittent theta-burst protocol will be implemented. This protocol is expected to modulate the excitability of the brain, priming it for a stronger activation of the motor-related brain areas engaged during brain-computer interface-based training. The structural MRI of each participant will be used to guide neuronavigation towards ipsilesional motor areas.
DEVICE	Sham rTMS	To implement a placebo stimulation, a sham coil will be used to deliver the same stimulation protocol. The sham coil is identical in dimensions and weight to the active coil but produces a diminished magnetic field. For the sham coil, the stimulation intensity is minimal beneath the center of the coil, the same area with the highest intensity during stimulation with an active coil. The structural MRI scan of each participant will be used to guide neuronavigation towards the same area where the active stimulation was applied.

Timeline

• Start date: 2023-11-08
• Primary completion: 2026-09-19
• Completion: 2027-09-19
• First posted: 2023-11-03
• Last updated: 2023-11-09

Locations

1 site across 1 country: Germany