Clinical trial NCT05511207: Clinical Validation of a Hybrid BCI-controlled FES for Upper Limb Rehabilitation After Stroke
Official title: RECOMmENceR: RE-establishing COrtico Muscular COMunication to ENhance Recovery. Clinical Validation of BCI-controlled Functional Electrical Stimulation for Upper Limb Rehabilitation After Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke Sequelae
Motor Disorders
Keywords: stroke
eeg
emg
cortico-muscular coherence
brain computer interface
Lead sponsor: I.R.C.C.S. Fondazione Santa Lucia
Sponsor class: OTHER
Collaborators: name: University of Roma La Sapienza
First posted: 2022-08-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients admitted to Fondazione Santa Lucia will be randomized in equal proportions between target intervention (RECOM) and control (CTRL)
Primary purpose: TREATMENT

Brief summary: The RECOMMENCER project aims at developing and testing a novel hybrid Brain Computer Interface device based on cortico-muscular connectivity, that will be employed to activate Functional Electrical Stimulation (FES) of upper limb muscles. After the technical implementation of the device and its preliminary testing on healthy subject, the investigators will evaluate the effects of a 1 month training with the device (RECOM) on post-stroke patients undergoing standard rehabilitation (add-on). The proposed intervention will be compared with an active physiotherapy training including FES (CTRL) which will be focused on upper limb with similar intensity as the target intervention (also delivered in add-on).

Detailed description: Brain-Computer Interface (BCI) systems for upper limb rehabilitation have proven some efficacy in the context of several randomized controlled trials (RCT). Such systems rely on the possibility reinforce motor-related brain activity (derived eg from electroencephalography, EEG) harnessing neuroplasticity phenomena ultimately leading to favorable motor outcome. Up to now, no hybrid BCI (hBCI) has been tested successfully for this purpose in a clinical trial. Hybrid BCIs include signals from the periphery (most commonly muscles, via surface electromyography, EMG) and are usually employed to improve BCI performances. In a rehabilitative context, the investigators aim to employ EMG signals to characterize common post-stroke abnormalities (spasticity, co-contractions, motor overflow) and possibly include those in a novel hBCI paradigm to promote both volitional control (EEG) over upper limb movement and "close to normal" muscular activation (EMG). To do so, the investigators propose cortico-muscular coherence (CMC) as a hybrid feature for BCI control. CMC is a measure of EEG-EMG synchronization during movement and has been described extensively in post-stroke patients in relation to their residual motor ability. With respect to previous literature, the proposed approach foresees the estimation of CMC as a multimodal integrated EEG-EMG network, comprising multiple EEG electrodes over the scalp bilaterally and several upper limb muscles bilaterally, so as to capture the above mentioned motor abnormalities (eg abnormal recruitment of non-target muscles). The investigators have already tested such feature on healthy subjects and stroke patients offline and verified its capability to detect upper limb movements online (studies published and/or submitted, see references). An already available BCI prototype was adapted with the parameters derived from such offline studies (see references). The RECOM intervention will be validated within a RCT (single blinded, for evaluators) on stroke patients undergoing rehabilitation (add-on). Before and after the intervention, all patients will undergo an extensive clinical evaluation (see outcome measures) and neurophysiological assessment. The latter will consist in a high density EEG-EMG recording during simple/complex upper limb movements. The recording will include a cinematic analysis (inertial measurement units - IMUs). The investigators hypothesize a better functional motor outcome in the affected upper limb for the RECOM group, which will be described by means of common clinical/functional scales combined with EEG/EMG and cinematic evaluation. Furthermore, aspects related to acceptability and usability of the novel system will be evaluated. In detail mood, motivation and satisfaction will be evaluated before (mood motivation) and after (satisfaction) each training session by means of Visual Analogue Scales; workload will be evaluated at the end of second and last training session by means of the Nasa-Task Load Index.

Eligibility criteria: Inclusion Criteria:

* unilateral stroke event at least 3 months before recruitment
* reduced strength in the upper limb

Exclusion Criteria:

* concomitant diseases affecting upper limb function
* spasticity in the upper limb (4-5 of MAS)
* severe neuropsychological deficit preventing active participation to the study
* contraindication to FES or EEG/EMG recording

Primary outcomes:
measure: Changes in Fugl-Meyer Assessment (FMA) - upper limb section
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Changes in Action Research Arm Test (ARAT)
timeFrame: Pre-Randomization, Post Training (within 48 hours)
Secondary outcomes:
measure: Changes in Modified Ashworth Scale for Spasticity (MAS)
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Changes Box and Block Test (BBT)
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Changes Numeric Rating Scale for pain in the upper limb (NRS)
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Changes in Manual Muscle Test (MMT) strength in upper limb segments
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Changes in NIH Stroke Scale
timeFrame: Pre-Randomization, Post Training (within 48 hours)
Other outcomes:
measure: Changes in EEG activity and connectivity
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Changes in EMG activation of target vs non target muscles.
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Changes in CMC
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Changes Cinematic parameters
timeFrame: Pre-Randomization, Post Training (within 48 hours)
Locations:
city: Rome
country: Italy
facility: Neurorehabilitation Units- Fondazione Santa Lucia, IRCCS
Study officials:
affiliation: Fondazione Santa Lucia, IRCCS
name: Floriana Pichiorri, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Roma La Sapienza
name: Jlenia Toppi, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pichiorri F, Morone G, Petti M, Toppi J, Pisotta I, Molinari M, Paolucci S, Inghilleri M, Astolfi L, Cincotti F, Mattia D. Brain-computer interface boosts motor imagery practice during stroke recovery. Ann Neurol. 2015 May;77(5):851-65. doi: 10.1002/ana.24390. Epub 2015 Mar 27.
citation: 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.
citation: Colamarino E, de Seta V, Masciullo M, Cincotti F, Mattia D, Pichiorri F, Toppi J. Corticomuscular and Intermuscular Coupling in Simple Hand Movements to Enable a Hybrid Brain-Computer Interface. Int J Neural Syst. 2021 Nov;31(11):2150052. doi: 10.1142/S0129065721500520. Epub 2021 Sep 30.
citation: Chen YT, Li S, Magat E, Zhou P, Li S. Motor Overflow and Spasticity in Chronic Stroke Share a Common Pathophysiological Process: Analysis of Within-Limb and Between-Limb EMG-EMG Coherence. Front Neurol. 2018 Oct 9;9:795. doi: 10.3389/fneur.2018.00795. eCollection 2018.
citation: Silva CC, Silva A, Sousa A, Pinheiro AR, Bourlinova C, Silva A, Salazar A, Borges C, Crasto C, Correia MV, Vilas-Boas JP, Santos R. Co-activation of upper limb muscles during reaching in post-stroke subjects: an analysis of the contralesional and ipsilesional limbs. J Electromyogr Kinesiol. 2014 Oct;24(5):731-8. doi: 10.1016/j.jelekin.2014.04.011. Epub 2014 May 9.
citation: von Carlowitz-Ghori K, Bayraktaroglu Z, Hohlefeld FU, Losch F, Curio G, Nikulin VV. Corticomuscular coherence in acute and chronic stroke. Clin Neurophysiol. 2014 Jun;125(6):1182-91. doi: 10.1016/j.clinph.2013.11.006. Epub 2013 Nov 16.
citation: Pichiorri F, Mattia D. Brain-computer interfaces in neurologic rehabilitation practice. Handb Clin Neurol. 2020;168:101-116. doi: 10.1016/B978-0-444-63934-9.00009-3.