Clinical trial NCT06951035: Impact of rTMS on BCI Control in Upper Limb Motor Rehabilitation of Patients With Chronic Stroke
Official title: ETUDE DE L'AMELIORATION DU CONTROLE DES INTERFACES CERVEAU-MACHINE PAR LA CONNECTIVITE FONCTIONNELLE ET LA STIMULATION MAGNETIQUE TRANSCRANIENNE REPETEE DANS LA REEDUCATION MOTRICE DU MEMBRE SUPERIEUR APRES UN ACCIDENT VASCULAIRE CHRONIQUE
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Chonic Stroke Patients With Motor Impairment of Upper Limb
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2025-04-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised Mutliple Baseline SCED.
Primary purpose: TREATMENT

Brief summary: Cerebrovascular accidents (strokes) are a major public health issue. Stroke is the 3rd leading cause of death and the leading cause of disability and loss of autonomy. In France, there are currently 130,000 new cases per year, and the aging of the population will lead to an increase in this number over the next few years. Among post-stroke impairments, motor deficit of the upper limb is the most common disability, affecting 73-88% of first-time stroke patients and 55-75% of chronic patients. Associated deficits can complicate rehabilitation management and affect recovery. The clinical profile of patients with motor deficits is therefore varied and complex, requiring an individualized approach. At present, only physiotherapy is recommended, with modest results.

Repeated transcranial magnetic stimulation is a therapy that can improve motor recovery, but currently has a low level of evidence according to the HAS (French Hight Health Authority), notably because of variability in efficacy due to heterogeneity in the clinical profile of patients. Nevertheless, it is still recommended for the recovery of cognitive functions, but also for resistant depression, and could be used to stimulate motor imagery (MI). MI training also has the advantage of stimulating the motor network. Difficult to achieve for a number of patients, the use of rTMS could facilitate this cognitive task and, in particular, provide better access to brain-computer interfaces (BCI). Indeed, among the innovative rehabilitation therapies, BCIs have emerged as the most promising. By translating brain activity during a cognitive task into a command such as electrical muscle stimulation, BCIs would restore the damaged motor network and induce motor recovery. The main obstacle to their widespread use in clinical practice is their lack of reliability, as almost 30% of patients are unable to control them correctly, either because of difficulty in performing the MI task, or because of difficulty in identifying a universal brain signature.

The BCINET project aims to improve the reliability of BCIs in two ways: by improving detection of the motor imagination task using new brain signatures, and through cognitive facilitation using rTMS.

1. - Using the dynamic communication of different brain areas during the MI task (or functional connectivity), we can identify patient-specific signatures. Studies of functional connectivity in healthy subjects performing an MI task without associated BCI have shown the interest of certain measures such as node degree or clustering coefficient. To find out whether functional connectivity parameters can be used in BCI algorithms, we will evaluate their effectiveness on an initial group of 5 patients to define their performance in discriminating the MI task and to determine their evolution over time in the absence of brain stimulation in stroke patients. Their initial study will also enable us to identify their evolution when TMS stimulation is applied.
2. - Cerebral magnetic stimulation could facilitate the MI task and enable better BCI rehabilitation for a number of patients. Two studies using either an inhibitory or excitatory stimulation protocol showed an improvement in spectral power signal and better discrimination of the MI task. However, the results were acquired using a single pre- and post-therapy measurement, and did not take into account behavioral variability in the use of BCIs or variability in TMS response according to patient profile. Therefore, in order to identify whether rTMS would improve BCI control, we would perform 9 Single-Case Experimental Design (SCED) studies in multiple baselines on a group of 5 patients according to 3 clinical profiles and 3 rTMS stimulation strategies. SCEDs are suitable experimental models for heterogeneous populations, particularly when the intervention presents some inter-individual variability in efficacy. They have the advantage of being able to demonstrate, on an individual scale, the effectiveness of the intervention on a small group of patients. Replication of the SCED allows us to increase the external validity of the intervention on sub-groups of patients (clinical severity, presence of associated hemineglect) and to study modifications in the interventional strategy (stimulation frequency, stimulation site).


Eligibility criteria: Inclusion Criteria:

* Single Stroke older than 6 months
* Distal motor deficit of the upper limb (UE-FMA score \< 53) with visible extension of the fingers (Medical Research Council (mRC) score ≥ 2)
* Right-handed
* Between 18 and 85 years of age
* Having given their written consent

Exclusion Criteria:

* Patient under tutorship or guardianship, under safeguard of justice, deprived of liberty, pregnant or breast feeding women
* Life-threatening pathologies or compromising follow-up during the study period
* Trouble of understanding : score below 12/15 in the Boston Diagnostic Aphasia Examination (BDAE) order execution test
* Fixed spasticity of finger or carpal flexors (mAS score = 4) or botulinum toxin injection less than 12 weeks old in the forearm or hand
* History of degenarative neurological pathology or craniectomy
* Deficient upper limb skin lesion preventing use of mucle stimulation
* Skin lesion of the scalp preventing EEG placement
* Participation in biomedical therapeutic research that may affect the recovery of the deficient hand during the study
* Patient who has previously participated in a therapeutic study rTMS (excluding single shock) or a BCI
* Patient who does not wish to be informed of a brain abnormality discovered accidentally on MRI

Primary outcomes:
measure: Measuring primary BCI performance
timeFrame: 6 weeks, 18 weeks
Secondary outcomes:
measure: Measuring secondary BCI performance by using the sensitivity indicator " recall "
timeFrame: Up to 20 weeks
measure: Measuring secondary BCI performance by using the positive predictive value " precision "
timeFrame: Up to 20 weeks
measure: Measuring secondary BCI performance by using the Run-Wise Cross-Validation method
timeFrame: Up to 20 weeks
measure: Assessment of the motor function using the Fugl-Meyer upper limb motor subscale (UE-FMA)
timeFrame: Inclusion visit, 6 weeks
measure: Assessment of the motor function using Box and Block Test (BBT)
timeFrame: Up to 20 weeks
measure: Assessment of the motor function using the Grip and Pinch force
timeFrame: Up to 20 weeks
measure: Evaluation of spasticity
timeFrame: Inclusion visit, 6 weeks
measure: Hemineglet assessment by text reading test
timeFrame: Up to 20 weeks
measure: Hemineglet assessment by line bissection test
timeFrame: Up to 20 weeks
measure: Analysis of spectral power
timeFrame: Up to 20 weeks
measure: Phase-Amplitude Coupling (PAC) analysis
timeFrame: Up to 20 weeks
measure: Quantification of the functional connectivity (FC)
timeFrame: 2 minutes before starting rTMS stimulation
measure: Measurement of cortical excitability (Motor Evoked Potentials)
timeFrame: Inclusion visit, 6 weeks, 18 weeks
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut du Cerveau
Study officials:
References: