Chronic Stroke Clinical Trial
Official title:
Repetitive Transcranial Magnetic Stimulation for Enhancing Brain Computer Interphase-induced Plasticity in Stroke: a Crossover Design
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.
Status | Recruiting |
Enrollment | 24 |
Est. completion date | September 19, 2027 |
Est. primary completion date | September 19, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 20 Years to 80 Years |
Eligibility | Inclusion Criteria: 1. Diagnosis of a subcortical stroke at least 6 months before the initiation of the trial and confirmed with magnetic resonance imaging (MRI) or computed tomography 2. Present moderate to severe hemiparesis in an upper limb 3. Language comprehension as well as visual and auditory perception sufficient to engage in Brain Computer Interface training 4. Age from 20 to 80 years old 5. Clear consciousness and stable vital signs 6. Eligible for MRI, EEG, BCI and TMS methods Exclusion Criteria: 1. Drug abuse or recent changes in medications that may alter the central nervous system when the measurements begin or during the measurements (e.g., benzodiazepines, serotoninergic and dopaminergic agents) 2. History of seizure 3. Bone, joint and muscle diseases 4. Peripheral neuropathy or other neurological or psychiatric diseases (including, tinnitus, migraine, or mood disorders with the exception of minimal, mild, and moderate depression, reflected as a Beck depression scale score lower than 29). 5. Strong cognitive deficits (including speech, attention, hearing, vision, sensation or intelligence deficits) reflected as a Montreal Cognitive Assessment (MoCA) score lower or equal to 24 6. Lesions in the upper extremities 7. Bone, joint and muscle diseases 8. Severe spasticity (higher than 3) or pain in the upper limb and affecting wrist extension 9. Contraindications of undergoing TMS examinations: history of seizures, history of epilepsy, unclear unconsciousness, migraines or metals on the head 10. Contraindications for MRI: metals in the body, metallic prosthetics or claustrophobia 11. Participation in other interventional trials using BCI or rTMS within less than 6 months ago 12. Participation in another interventional clinical trial 13. Suspected lack of compliance 14. Pregnant or nursing women |
Country | Name | City | State |
---|---|---|---|
Germany | Max Planck Institute for Human Cognitive and Brain Sciences | Leipzig | Saxony |
Lead Sponsor | Collaborator |
---|---|
Max Planck Institute for Human Cognitive and Brain Sciences | University of Halle Medical Faculty |
Germany,
Peng Y, Wang J, Liu Z, Zhong L, Wen X, Wang P, Gong X, Liu H. The Application of Brain-Computer Interface in Upper Limb Dysfunction After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Hum Neurosci. 2022 Mar 29;16:798883. doi: 10.3389/fnhum.2022.798883. eCollection 2022. — View Citation
Tang Z, Han K, Wang R, Zhang Y, Zhang H. Excitatory Repetitive Transcranial Magnetic Stimulation Over the Ipsilesional Hemisphere for Upper Limb Motor Function After Stroke: A Systematic Review and Meta-Analysis. Front Neurol. 2022 Jun 20;13:918597. doi: 10.3389/fneur.2022.918597. eCollection 2022. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Adherence | Number of missed sessions per participant | Through study completion, for 25 days. | |
Other | Upper extremity motor activity log (UE-MAL) | The UE-MAL is a questionnaire that inspects how much and how well the participant uses their paretic arm during activities of daily living. Participants are asked standardized questions about how often they use their more-affected arm for different activities (Amount Scale or AS) and the perceived quality of their movements when executing such tasks (How Well Scale or HW). The evaluations are done on a scale from 0 to 5. 0 represents non-use and 5 is use equal to the non- paretic hand. The scores' explanations are printed on separate sheets of paper and are placed in front of the participant during the test administration. The sums of values recorded before and after the stimulation periods will be fed into an unpaired sample t-test to evaluate carryover effects whereas the differences observed between recordings before and after the stimulation will be fed into an unpaired sample t-test for the evaluation of initial evidence of the effect of rTMS. | Measured one time per day, at days 2, 13, 14, and 25. | |
Other | Withdrawal rate | The proportion of participants that drop out. | Through study completion, for 25 days. | |
Other | Last item of the stroke impact scale (SIS) | The last item of the SIS will be used to ask participants to rank of their expected improvement due to the intervention from 0 to 100. This assessment will be used also after stimulation to assess the perceived improvement. The sums of values recorded before and after the stimulation periods will be fed into an unpaired sample t-test to evaluate carryover effects whereas the differences observed between recordings before and after the stimulation will be fed into an unpaired sample t-test for the evaluation of initial evidence of the effect of rTMS. | Measured once per day, at days 2, 13, 14, and 25. | |
Other | Micro fractional anisotropy (micro-FA) | Micro-FA is a proxy of white matter integrity that in contrast with FA can resolve ambiguities caused by crossing fibers. Micro-FA values will be obtained by acquiring diffusion-weighted images with a free waveform encoding pulse sequence. The micro-FA will be evaluated in the area of stimulation and areas that show changes in FA, in order to further characterize micro-structural arrangements elicited by the brain stimulation. A second-order cumulative model will be implemented for analysis. | Measured once per day, at days 2, 13, 14, and 25. | |
Other | Glial fibrillary acidic protein (GFAP) | GFAP will be explored as it is proposed to change with plasticity due to the transient swelling of astrocytes during structural neuronal plasticity. The investigators expect a higher change in GFAP levels after active stimulation in comparison with after placebo. | Measured twice per day, at the days 3, 12, 15 and 24. The first measure occurs before the intervention and the second measure after the intervention. | |
Other | Neurofilaments (light chain) | Neurofilament light chains in blood will be inspected as they have been proposed as a marker of recovery after stroke. The investigators expect a higher change in Neurofilaments levels after active stimulation in comparison with after placebo. | Measured twice per day, at the days 3, 12, 15 and 24. The first measure occurs before the intervention and the second measure after the intervention. | |
Other | Beta-synuclein | Beta-synuclein will be explored because it has been proposed as a marker of synaptic alterations. The investigators expect a higher change in Beta-synuclein levels after active stimulation in comparison with after placebo. | Measured twice per day, at the days 3, 12, 15 and 24. The first measure occurs before the intervention and the second measure after the intervention. | |
Primary | Motor-evoked potential (MEP) parameters | An MEP is the electromyography response to a single TMS pulse delivered over the motor cortex, over the representation of multiple muscles. MEP changes will be evaluated with a mixed effects model. mixed-effects model. The model will consider the Patient, Period, Treatment (stimulation type) and Session number. The Period*Treatment interaction will be verified to detect carry-over effects. The investigators expect to observe a main effect of Treatment and Session number. | Measured two times per day, at the days: 3-12 and 15-24. The first measurement is performed immediately before the rTMS-BCI intervention and the second immediately after the rTMS-BCI intervention. | |
Primary | Fugl-Meyer upper extremity assessment of sensorimotor function | Quantitative evaluation of motor, balance, sensation and joint functions. The sums of values recorded before and after the stimulation periods will be fed into an unpaired sample t-test to evaluate carryover effects whereas the differences observed between recordings before and after the stimulation will be fed into an unpaired sample t-test for the evaluation of initial evidence of the effect of rTMS. | Measured one time at day, at the days: 2, 13, 14, and 25. | |
Primary | Event-related desynchronization (ERD) | Electroencephalography (EEG) will be recorded during a cued motor task. This data will be used to calculate event-related de-synchronization, defined as the difference in signal power in the miu (8-12 Hz) and beta bands (13-30 Hz) between a baseline period prior to the cue and a post-cue period. Changes in ERD will be evaluated with permutation-based statistics. | Measured one time per day, at the days: 2, 13, 14, and 25. | |
Secondary | Brain-Computer Interface accuracy | Ratio of correct trials over the total number of trials, as a proxy of performance during brain-computer interface based training. BCI accuracy will be evaluated with a mixed-effects model. mixed-effects model. The model will consider the Patient, Period, Treatment (stimulation type) and Session number. The Period*Treatment interaction will be verified to detect carry-over effects. The investigators expect to observe a main effect of Treatment and Session number. | Measured one time per day, at days 3-12 and days 15-24. | |
Secondary | Task-related functional Magnetic Resonance Imaging (t-fMRI) | fMRI will be acquired during a motor task. The fMRI acquired during the task will be used to evaluate blood-oxygen-level-dependent (BOLD) signal changes after the active stimulation over the motor areas: premotor cortex (PMC), motor cortex (M1), supplementary motor area (SMA), cerebellum and basal ganglia; and this change will be compared with the change after placebo stimulation. In addition, the investigators will explore whether changes in BOLD signal in areas involved in BCI training can be observed after active stimulation, reflecting a potential enhancement of BCI effects. Changes in fMRI will be evaluated with a mixed-effects model in a whole-brain analysis. | Measured one time per day, at the days 2, 13, 14, and 25. | |
Secondary | Jebsen-Taylor Hand Function Test | Clinical assessment of hand function that consists of 7 tasks: staking checkers, feeding, manipulating and lifting objects, writing, and page-turning. The sums of values recorded before and after the stimulation periods will be fed into an unpaired sample t-test to evaluate carryover effects whereas the differences observed between recordings before and after the stimulation will be fed into an unpaired sample t-test for the evaluation of initial evidence of the effect of rTMS. | Measured one time per day, at the days 2, 13, 14, and 25. | |
Secondary | Diffusion-based tractography | Evaluation of fractional anisotropy (FA) as a proxy of white matter changes. Diffusion-weighted images will be used to used to calculate FA. FA reflects the deviation of random diffusion of water molecules in a voxel. Analysis of effects in diffusion will be carried out at the whole brain level and using contrast weights in a flexible factorial design with multiple groups of subjects. | Measured one time per day, at the days 2, 13, 14, and 25. | |
Secondary | Movement-related cortical potential amplitude | Electroencephalography (EEG) will be recorded during a cued-motor task. The EEG data will be align according to the onset of the cue and averaged across trials at each time point to obtain the movement related cortical potential curves. Peak amplitudes will be compared before and after the 10 sessions of active stimulation and before and after the 10 sessions of placebo stimulation using permutation based statistics. | Measured one time per day, at the days 2, 13, 14, and 25. | |
Secondary | Resting-state functional Magnetic Resonance Imaging (rs-fMRI) | In addition, the fMRI during rest will be used to analyze the connectivity between motor-related. Changes in connectivity will be explored and measured by calculation of global correlation, local correlation, amplitude low-frequency fluctuations, intrinsic connectivity and fractional amplitude low-frequency fluctuations. In addition, a seed-based analysis will be performed to check for changes in connectivity between the area of stimulation and other motor areas: M1, SMA, cerebellum and basal ganglia. | Measured one time per day, at the days 2, 13, 14, and 25. | |
Secondary | Voxel-based morphometry | Voxel-based morphometry is a proxy of gray matter concentration changes based on T1-weighted MRI. This will be evaluated in response to active and placebo stimulation. A flexible factorial design will address potential changes in grey matter after the stimulation. The investigators hypothesize that changes in gray matter will be observed for the stimulated region and functionally connected areas as M1, contralateral PMC, SMA, cerebellum and basal ganglia. | Measured one time per day, at the days 2, 13, 14, and 25. | |
Secondary | Brain-derived neurotrophic factor (BDNF) in serum | Serum BDNF is proposed as a marker of plasticity mechanisms. Previous studies suggest that BDNF can be modulated by multiple-session rTMS protocols. However, no study has explored changes in BDNF after excitatory rTMS protocols in stroke participants. The investigators expect a higher change in BDNF levels after active stimulation in comparison with after placebo. | Measured twice per day, at the days 3, 12, 15 and 24. The first measure occurs before the intervention and the second measure after the intervention. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03780296 -
Implementing Technology Enhanced Real Time Action Observation Therapy in Persons With Chronic Stroke
|
N/A | |
Not yet recruiting |
NCT06057584 -
Effect of Somatosensory Motor Intergration Training on Post-stroke Upper Limb Function.
|
N/A | |
Completed |
NCT03228264 -
A Trial Investigating Telerehabilitation as an add-on to Face-to-face Speech and Language Therapy in Post-stroke Aphasia.
|
N/A | |
Completed |
NCT03531567 -
Game-Based Home Exercise Programs in Chronic Stroke: A Feasibility Study
|
N/A | |
Completed |
NCT02364232 -
Effects of Home-based vs. Clinic-based Rehabilitation on Sensorimotor, Cognition, Daily Function, and Participation
|
N/A | |
Completed |
NCT04121754 -
Post-Stroke Walking Speed and Community Ambulation Conversion Study
|
N/A | |
Completed |
NCT04574687 -
Effects of Action Observation Therapy on Fine Motor Skills of Upper Limb Functions in Chronic Stroke Patients.
|
N/A | |
Recruiting |
NCT04534556 -
Wireless Nerve Stimulation Device To Enhance Recovery After Stroke
|
N/A | |
Recruiting |
NCT04974840 -
Thera-band Resisted Treadmill Training for Chronic Stroke Patients
|
N/A | |
Completed |
NCT04553198 -
Quantifying the Role of Sensory Systems Processing in Post-Stroke Walking Recovery
|
N/A | |
Completed |
NCT04226417 -
Effect of Home Based Transcranial Direct Current Stimulation (tDCS) With Exercise on Upper and Lower Limb Motor Functions in Chronic Stroke
|
N/A | |
Recruiting |
NCT06049849 -
Can Patients With Chronic Stroke Regain Living Independence by Daily Energizing With Biophoton Generators
|
N/A | |
Active, not recruiting |
NCT02881736 -
Proprioceptive Deficits and Anomalies in Movement-error Processing in Chronic Stroke Patients
|
N/A | |
Completed |
NCT03208634 -
Rehabilitation Multi Sensory Room for Robot Assisted Functional Movements in Upper-limb Rehabilitation in Chronic Stroke
|
N/A | |
Completed |
NCT05183100 -
Effects of Neurodynamics on Lower Extremity Spasticity - a Study in Chronic Stroke
|
N/A | |
Completed |
NCT03326349 -
Home-based Computerized Cognitive Rehabilitation in Chronic Stage Stroke
|
N/A | |
Recruiting |
NCT04721860 -
Optimizing Training in Severe Post-Stroke Walking Impairment
|
N/A | |
Recruiting |
NCT06051539 -
Outcomes and Health Economics of Stroke Using Rhythmic Auditory Stimulation
|
N/A | |
Not yet recruiting |
NCT06060470 -
Active Balance and Cardio Care Intervention on Physical and Cardiovascular Health in People With Chronic Stroke
|
N/A | |
Recruiting |
NCT05591196 -
Hand and Arm Motor Recovery Via Non-invasive Electrical Spinal Cord Stimulation After Stroke
|
N/A |