Clinical trial NCT05637775: DiSCIoser: Improving Arm Sensorimotor Functions After Spinal Cord Injury Via Brain-Computer Interface Training
Official title: DiSCIoser: Unlocking Recovery Potential of Arm Sensorimotor Functions After Spinal Cord Injury by Promoting Activity-dependent Brain Plasticity and Modeling the Causal Relationship Between Brain Plasticity and Recovery of Function
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Motor Disorders
Keywords: spinal cord injury
brain computer interface
motor imagery
motor rehabilitation
neurorehabilitation
brain plasticity
Lead sponsor: I.R.C.C.S. Fondazione Santa Lucia
Sponsor class: OTHER
Collaborators: name: University of Roma La Sapienza
First posted: 2022-12-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible subacute cervical SCI patients admitted to Fondazione Santa Lucia Hospital for standard rehabilitation care will be randomized in equal proportions (1:1 ratio) between BCI-assisted MI training- EXP) and Control (MI without BCI - CTRL).
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to validate the efficacy of a Brain-Computer Interface (BCI)-based intervention for hand motor recovery in subacute cervical spinal cord injured (SCI) patients during rehabilitation. The study will provide evidence for the clinical/neurophysiological efficacy of the BCI intervention as a means to promote cortical sensorimotor plasticity (remote plasticity) and thus maximize recovery of arm functions in subacute cervical SCI. Participants will undergo an extensive clinical, neurophysiological, neuropsychological and neuroimaging assessment before and after a BCI training based on motor Imagery (MI) of hands. The intervention will be delivered with a system that was originally validated for stroke patients and adapted to the aims of this study. Researchers will compare the BCI intervention with an active MI training without BCI support (active comparator).

Detailed description: Despite its relatively low incidence SCI represents a devastating chronic condition for which there is still no cure or consistent approach for intervention. Cervical SCI tremendously affects the quality of life since the use of the upper extremities is critical for completing basic activities of daily living. Extensive research conducted on SCI animal models and humans has revealed that cortical and subcortical reorganization (ie., remote plasticity) takes place after SCI and it is associated with recovery of sensorimotor function (in humans the relevance of these aspect has been mainly emphasised in incomplete SCI). Current rehabilitation after traumatic SCI mainly consists of intensive training of lost/impaired function that is assumed to augment activity-dependent plasticity of spared circuits and thus, leading to functional improvements. Recently, neuromodulatory interventions targeting the sensorimotor systems at various levels has been applied in humans with SCI in combination with training to enhance functional recovery. Neurological rehabilitation of SCI can also benefit of cognitive training based on MI, that enables active stimulation of brain motor areas promoting brain plasticity associated with positive effects on motor performance. In the effort of encouraging the top-down contribution of supraspinal sensorimotor signaling in SCI rehabilitation, the BCI technology may provide for fundamental tools not only for restoring but even recovering sensorimotor function. The long history of BCI research in SCIs has been substantially devoted to develop systems to control external devices to restore function. However, recent findings indicate that non invasive BCI training in combination with intensive rehabilitation can be beneficial to chronic SCI patients for gait, as well as arm function recovery. The current study relies on the hypothesis that monitoring and modulating brain plasticity occurring as a consequence of a SCI is a key factor in shaping clinically valuable top-down rehabilitation strategies that target the recovery of sensorimotor function in patients with SCI. To ground such vision, the researchers will use a goal-oriented action imagery training which is controlled and objectified by a BCI as a means to engage sensorimotor system and thus to facilitate neuroplasticity and optimize functional recovery in SCI during the subacute phase in which brain and spinal plasticity is at its climax.

In this study researchers will test the superiority of a BCI-assisted MI training (up to 12 weeks duration) with respect to MI practiced without BCI feedback (similar training setting and duration) to promote recovery of sensorimotor functions in traumatic cervical SCI subjects. The main hypothesis is that establishing a real-time contingency between the content of MI and an ecological feedback specifically designed to train MI in SCI patients will boost the effect of MI training in engaging the sensorimotor system. Primary and secondary outcome measures (reported in the dedicated section) include the most commonly used clinical and functional scales to assess SCI patients recovery. Neurophysiological and Neuroimaging outcomes are reported as other outcome measures in the dedicated session. Neuropsychological evaluation will include Test of Attentional Performance (TAP), Stroop Test, Trail Making Test (TMT), assessment of depression and anxiety; body ownership and representation. Furthermore, motivation, satisfaction, workload and usability will be evaluated along training.

Eligibility criteria: Inclusion Criteria:

* subacute cervical SCI (30-90 days from event)
* classification according to ISNCSCI AIS A-D, lesion level C1-T1
* Upper Extremity Motor Score (UEMS) \< 40

Exclusion Criteria:

* other conditions (present or previous) potentially affecting sensorimotor upper limb function
* inability to give informed consent and understand the requirements for the training

Primary outcomes:
measure: Mean change from baseline on Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) somatosensory scores of bilateral arms at end of intervention
timeFrame: Pre-Randomization, Post Training (within 48 hours)
Secondary outcomes:
measure: Mean change from baseline on Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) motor scores of bilateral arms at end of intervention
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Mean change from baseline in the Spinal Cord Injury Independence Measure (SCIM) - self care section
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Mean change in Pain as assessed by the International SCI Pain Basic Dataset (ISCIPBDS)
timeFrame: Pre-Randomization, Post Training (within 48 hours)
measure: Mean change in Upper Extremity Motor Score (UEMS) from the ISNCSCI AIS evaluation
timeFrame: Pre-Randomization, Post Training (within 48 hours)
Other outcomes:
measure: Changes from baseline on high density Electroencephalography (hdEEG) patterns of cortical oscillatory activity and connectivity at end of intervention.
timeFrame: Pre-Randomization, Post Training (within 1 week)
measure: Changes in Motor Evoked Potentials (MEPs)
timeFrame: Pre-Randomization, Post Training (within 1 week)
measure: Changes in Somatosensory Evoked Potentials (SSEPs)
timeFrame: Pre-Randomization, Post Training (within 1 week)
measure: Structural Magnetic Resonance Imaging (MRI) of the whole brain and spinal cord
timeFrame: Pre-Randomization, Post Training (within 1 week)
Locations:
city: Rome
country: Italy
facility: Neurorehabilitation Units- Fondazione Santa Lucia, IRCCS
Study officials:
affiliation: Fondazione Santa Lucia, IRCCS
name: Donatella Mattia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione Santa Lucia, IRCCS
name: Giorgio Scivoletto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Roma La Sapienza
name: Febo Cincotti, MD, PhD
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: Donati AR, Shokur S, Morya E, Campos DS, Moioli RC, Gitti CM, Augusto PB, Tripodi S, Pires CG, Pereira GA, Brasil FL, Gallo S, Lin AA, Takigami AK, Aratanha MA, Joshi S, Bleuler H, Cheng G, Rudolph A, Nicolelis MA. Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients. Sci Rep. 2016 Aug 11;6:30383. doi: 10.1038/srep30383.
citation: Brown AR, Martinez M. From cortex to cord: motor circuit plasticity after spinal cord injury. Neural Regen Res. 2019 Dec;14(12):2054-2062. doi: 10.4103/1673-5374.262572.
citation: Mattia D, Pichiorri F, Colamarino E, Masciullo M, Morone G, Toppi J, Pisotta I, Tamburella F, Lorusso M, Paolucci S, Puopolo M, Cincotti F, Molinari M. The Promotoer, a brain-computer interface-assisted intervention to promote upper limb functional motor recovery after stroke: a study protocol for a randomized controlled trial to test early and long-term efficacy and to identify determinants of response. BMC Neurol. 2020 Jun 27;20(1):254. doi: 10.1186/s12883-020-01826-w.