BCI-assisted MI Intervention in Subacute Stroke

Stroke Clinical Trial

— Promotoer  

Official title:

The PROMOTOER: a BCI -Based Intervention That Promotes Upper Limb Functional Motor Recovery. A Randomized Clinical Trial to Test Long-term Efficacy and to Identify Determinants of Response to Intervention in Subacute Stroke Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04353297
• Other study ID #: RF-2018-12365210
• Status: Completed
• Phase: N/A
• Start date: January 28, 2021
• Est. completion date: December 1, 2023

Study information

• Verified date: February 2024
• Source: I.R.C.C.S. Fondazione Santa Lucia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Stroke is a leading cause of long-term disability. Cost-effective post-stroke rehabilitation programs are critically needed. Brain-Computer Interface (BCI) systems which enable the modulation of EEG sensorimotor rhythms are promising tools to promote early improvements of motor rehabilitation outcomes after stroke. This project intends to boost this BCI application beyond the state of art by providing: i) evidence for a short/long-term efficacy in enhancing post-stroke functional hand motor recovery; and ii) quantifiable indices (beyond clinical scales) sensitive to stroke participant's response to a Promotoer (BCI system compatible with clinical setting) -based intervention. To these aims, a longitudinal randomized controlled trial will be performed in which, subacute stroke participants will undergo a Promotoer- assisted hand motor imagery training.

Description:

Stroke is a major public health and social care concern worldwide, being the leading cause of long-term disability in adults. The upper limb motor impairment commonly persists after stroke affecting patients' everyday life functional independence. Despite the intensive rehabilitation, the variability in the nature and the extent of upper limb recovery remains a crucial factor effecting rehabilitation outcomes. Electroencephalography (EEG) -based Brain Computer Interface (BCI) technology is a potential tool to promote functional motor recovery of upper limbs after stroke as shown in several randomized controlled trials. The investigators' multidisciplinary team was successful in designing, implementing and clinically validating a sensorimotor rhythm-based BCI combined with realistic visual feedback of upper limb to support hand motor imagery (MI) practice in stroke participants. However, important questions remain to be addressed to translate BCI in clinical practice such as defining whether the expected BCI-induced early improvements in functional motor outcomes can be sustained in a long-term after stroke. This requires advancements in the knowledge on brain functional re-organization after stroke and how this re-organization would correlate with the functional motor outcome (evidence-base medicine). Last but not least, the definition of the determinants of the patient response to-treatment is paramount to optimize the process of personalized medicine in rehabilitation. The fundamental of this project stems from the investigators' previous findings on the efficacy of BCI-assisted MI training in subacute stroke participants. These promising findings corroborated the idea that a relatively low-cost technique (i.e. EEG-based BCI) can be exploited to deliver a rehabilitative intervention (in this case MI) and prompted the research team to undertake a further translational effort by implementing an all-in-one BCI-supported MI training station- the Promotoer. In this project, the investigators will provide evidence for a persistency (up to 6 months) of the significant early improvement of hand motor function induced by the BCI-assisted MI training operated via the Promotoer. Task-specific training was recently reported to induce long-term improvements (6 months follow-up) in arm motor function after stroke. Thus, the hypothesis is that the BCI-based rewarding of hand MI tasks would promote long-lasting retention of early induced positive effect on motor performance with respect to MI task practiced in an open loop condition (i.e., without BCI). Further hypothesis is that such clinical improvement would be sustained by a long-lasting neuroplasticity changes that would be harnessed by the BCI -based intervention. This hypothesis rises from current evidence for an early enhancement of post-stroke plastic changes enabled by BCI- based trainings. To test this hypothesis, a longitudinal assessment of the brain network organization derived from advanced EEG signal processing will be performed. The heterogeneity of stroke makes prediction of treatment responder a great challenge. The investigators hypothesize that the longitudinal functional and neurophysiology assessment over 6 months from the intervention will allow for insights in biomarkers and potential predictors of stroke participants' response to the Promotoer training. Some of the well-recognized factors contributing to functional motor recovery after stroke such as the relation between lesion characteristics and patterns of post-stroke motor cortical re-organization (e.g., ipsilesional/contralesional primary and non-primary motor areas; cortico-spinal tract integrity, severity of motor deficits at baseline) will be taken into account.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 1, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• first ever unilateral stroke - confirmed by MRI;
• hemiplegia/hemiparesis from 1 to 6 months since stroke;
• age between 18 and 80 years;

Exclusion Criteria:

• severe neglect and aphasia;
• dementia;
• severe spasticity - Modified Ashworth Scale >4 at shoulder/elbow/wrist;
• Upper Extremity Fugl-Meyer Assessment (UE-FMA) >47/60 score (60 is without considering 6 score point for tendon reflexes);
• Token test >29 score;
• concomitant neurological disorders

Related Conditions & MeSH terms

• Motor Disorders
• Stroke

Intervention

Other:
• EEG-based BCI system for (hand) Motor Imagery training
The Promotoer is an all-in-one BCI-supported motor imagery (MI) training station, equipped with a computer, a commercial wireless Electroencephalography (EEG)/ Electromyography (EMG) system, a screen for therapist feedback (EEG and EMG activity monitoring) and screen for the real-time ecological feedback to patient - a custom software program that provides a for (personalized) visual representation of the patient's own hands. As such, this software allows the therapists to create an artificial reproduction of a given patient's hand/forearm by adjusting a digitally created image in shape, size, skin colour and orientation to match as much as possible the real patient hand/forearm. Training consists of the MI tasks only of the affected hand, grasping or finger extension in separate runs. The trial length will include a constant baseline period of 4 sec and a task period of maximally 10 sec for BCI intervention group. Each training session will consist of 4 runs (20 trials each).
• Motor Imagery training
Training consists of MI tasks only of the affected hand, grasping or finger extension in separate runs. MI training will be delivered without BCI support (ie., the Promotoer system will not provide real-time feedback of MI performance; hand/forearm visual representation will remain standstill) with a dose/setting regimen equivalent to EXP intervention. The trial length will include a constant baseline period of 4 sec and a task period of maximally 4 sec. Each training session will consist of 4 runs (20 trials each).

Locations

Country	Name	City	State
Italy	Neurorehabilitation Units- Fondazione Santa Lucia, IRCCS	Rome

Sponsors (3)

Lead Sponsor	Collaborator
I.R.C.C.S. Fondazione Santa Lucia	Istituto Superiore di Sanità, University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

References & Publications (11)

Biasiucci A, Leeb R, Iturrate I, Perdikis S, Al-Khodairy A, Corbet T, Schnider A, Schmidlin T, Zhang H, Bassolino M, Viceic D, Vuadens P, Guggisberg AG, Millan JDR. Brain-actuated functional electrical stimulation elicits lasting arm motor recovery after — View Citation

Cervera MA, Soekadar SR, Ushiba J, Millan JDR, Liu M, Birbaumer N, Garipelli G. Brain-computer interfaces for post-stroke motor rehabilitation: a meta-analysis. Ann Clin Transl Neurol. 2018 Mar 25;5(5):651-663. doi: 10.1002/acn3.544. eCollection 2018 May. — View Citation

Cincotti F, Pichiorri F, Arico P, Aloise F, Leotta F, de Vico Fallani F, Millan Jdel R, Molinari M, Mattia D. EEG-based Brain-Computer Interface to support post-stroke motor rehabilitation of the upper limb. Annu Int Conf IEEE Eng Med Biol Soc. 2012;2012: — View Citation

Coupar F, Pollock A, Rowe P, Weir C, Langhorne P. Predictors of upper limb recovery after stroke: a systematic review and meta-analysis. Clin Rehabil. 2012 Apr;26(4):291-313. doi: 10.1177/0269215511420305. Epub 2011 Oct 24. — View Citation

Fleming MK, Sorinola IO, Roberts-Lewis SF, Wolfe CD, Wellwood I, Newham DJ. The effect of combined somatosensory stimulation and task-specific training on upper limb function in chronic stroke: a double-blind randomized controlled trial. Neurorehabil Neur — View Citation

Kantak SS, Stinear JW, Buch ER, Cohen LG. Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury. Neurorehabil Neural Repair. 2012 Mar-Apr;26(3):282-92. doi: 10.1177/1545968311 — View Citation

Kim AS, Cahill E, Cheng NT. Global Stroke Belt: Geographic Variation in Stroke Burden Worldwide. Stroke. 2015 Dec;46(12):3564-70. doi: 10.1161/STROKEAHA.115.008226. Epub 2015 Oct 20. No abstract available. — View Citation

Morone G, Pisotta I, Pichiorri F, Kleih S, Paolucci S, Molinari M, Cincotti F, Kubler A, Mattia D. Proof of principle of a brain-computer interface approach to support poststroke arm rehabilitation in hospitalized patients: design, acceptability, and usab — View 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.2 — View Citation

Ramos-Murguialday A, Broetz D, Rea M, Laer L, Yilmaz O, Brasil FL, Liberati G, Curado MR, Garcia-Cossio E, Vyziotis A, Cho W, Agostini M, Soares E, Soekadar S, Caria A, Cohen LG, Birbaumer N. Brain-machine interface in chronic stroke rehabilitation: a con — View Citation

Stinear CM, Barber PA, Smale PR, Coxon JP, Fleming MK, Byblow WD. Functional potential in chronic stroke patients depends on corticospinal tract integrity. Brain. 2007 Jan;130(Pt 1):170-80. doi: 10.1093/brain/awl333. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes from baseline on high density Electroencephalography (hdEEG) patterns of cortical oscillatory activity and connectivity at end of intervention and follow-up	EEG recordings (motor relevant oscillatory activity and functional connectivity to evaluate the neurophysiological substrates of the experimental intervention efficacy, in both BCI-based and Control intervention groups at end of treatment and follow-up time points	End of treatment at 48-hours post-intervention (T1) and up to 6 month follow-up: T2 (1 month post-intervention), T3 (3 months post-intervention), and T4 (6 months post-intervention)
Other	Structural Magnetic Resonance Imaging (MRI) of the whole brain	structural MRI to evaluate lesion size/site and white matter alteration in both experimental and Control groups as factor influencing experimental intervention response	After randomization/before beginning of treatment (T0) and at 3 months follow-up (T3)
Other	Motor Evoked Potentials (MEPs) upper limbs	MEPs elicited via Transcranial Magnetic Stimulation (TMS) to evaluate the integrity of the Cortico Spinal Tract (CST) in both experimental and Control groups as factor influencing experimental intervention response	After randomization/before beginning of treatment (T0)
Other	Test for Attentional Performance (TAP) at baseline	TAP (3 items: alertness, sustained attention and working memory) to evaluate attention participant profile in both experimental and control groups as a factor influencing experimental intervention response	At screening for inclusion
Primary	Mean change from baseline on the Fugl-Meyer scores for Upper Extremity-Motor Control at end of intervention	Fugl-Meyer scores for Upper Extremity-Motor Control (range from 0- minimum to 66-maximum points where 66-maximum is normal) [International Classification Function: body function] assessed in both BCI-based and Control intervention groups (superiority of BCI-based intervention vs Control intervention in improving hand motor function outcome)	End of treatment at 48-hours post-intervention (T1)
Secondary	Mean change from T1 on Fugl-Meyer scores for Upper Extremity-Motor Control [International Classification Function: body function] at 6 months follow-up	Fugl-Meyer scores for Upper Extremity-Motor Control (range from 0- minimum to 66-maximum points, where 66-maximum is normal) [International Classification Function: body function] assessed in both BCI-based and Control intervention groups at follow-up time points (long-term efficacy of BCI -based intervention)	Up to 6 month follow-up: T2 (1 month post-intervention), T3 (3 months post-intervention), and T4 (6 months post-intervention)
Secondary	Minimal Clinical Important Difference (MCID) at Fugl-Meyer Upper Extremity	Proportion of the patients that will achieve the MCID at Fugl-Meyer Upper Extremity Motor , in BCI -intervention Group Vs Control- intervention Group.	Up to 6 month follow-up: T2 (1 month post-intervention), T3 (3 months post-intervention), and T4 (6 months post-intervention)
Secondary	Mean change from baseline on Modified Ashworth Scale (MAS) at end of intervention and follow-up	Measure of arm spasticity (at shoulder + elbow + hand) as measured by means of MAS (score from 0 to 5 points, where 0 is equal to absence of spasticity, 5 is equal to high degree of spasticity)	End of treatment at 48-hours post-intervention (T1) and up to 6 month follow-up: T2 (1 month post-intervention), T3 (3 months post-intervention), and T4 (6 months post-intervention)
Secondary	Mean change from baseline on Numeric Rating Scale for pain in the affected arm	Measure of arm perceived pain by means of Numeric Rating Scale (score from 0 to 10 points where 0 is equal to NO PAIN and 10 is equal to UNSPEAKABLE PAIN)	End of treatment at 48-hours post-intervention (T1) and up to 6 month follow-up: T2 (1 month post-intervention), T3 (3 months post-intervention), and T4 (6 months post-intervention)
Secondary	Mean change from baseline on Action Research Arm Test (ARAT) at end of intervention and follow-up	ARAT assessed in both BCI-based and Control intervention groups at end of treatment and follow-up time points (long-term efficacy of BCI -based intervention)	End of treatment at 48-hours post-intervention (T1) and up to 6 month follow-up: T2 (1 month post-intervention), T3 (3 months post-intervention), and T4 (6 months post-intervention)
Secondary	Mean change from baseline on National Institute of Health Stroke Scale (NIHSS) at end of intervention and follow-up	Measure of severity of stroke symptoms as for the National Institute of Health Stroke Scale-NIHSS (composed by 11 items with a total score ranging from 0 to a maximum depending on each item, where 0 is normal and maximum is pathological response)	End of treatment at 48-hours post-intervention (T1) and up to 6 month follow-up: T2 (1 month post-intervention), T3 (3 months post-intervention), and T4 (6 months post-intervention)
Secondary	Mean change on Manual Muscle Test (MMT) for affected arm at end of intervention and follow-up	MMT for affected arm shoulder/elbow/wrist (flexor/extensor muscles) in both BCI-based and Control intervention groups at end of treatment and follow-up time points (long-term efficacy of BCI -based intervention)	End of treatment at 48-hours post-intervention (T1) and up to 6 month follow-up: T2 (1 month post-intervention), T3 (3 months post-intervention), and T4 (6 months post-intervention)