Brain-controlled Spinal Cord Stimulation in Patients With Spinal Cord Injury

Study Overview
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Brief Summary
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In a current first-in-human study, called Stimulation Movement Overground (STIMO, NCT02936453), Epidural Electrical Stimulation (EES) of the spinal cord is applied to enable individuals with chronic severe spinal cord injury (SCI) to complete intensive locomotor neurorehabilitation training. In this clinical feasibility study, it was demonstrated that EES results in an immediate enhancement of walking function, and that when applied repeatedly as part of a neurorehabilitation program, EES can improve leg motor control and trigger neurological recovery in individuals with severe SCI to a certain extent (Wagner et al. 2018). Preclinical studies showed that linking brain activity to the onset and modulation of spinal cord stimulation protocols not only improves the usability of the stimulation, but also augments neurological recovery. Indeed, rats rapidly learned to modulate their cortical activity in order to adjust the amplitude of spinal cord stimulation protocols. This brain-spine interface allowed them to increase the amplitude of the movement of their otherwise paralyzed legs to climb up a staircase (Bonizzato et al. 2018). Moreover, gait rehabilitation enabled by this brain-spine interface (BSI) augmented plasticity and neurological recovery. When EES was correlated with cortical neuron activity during training, rats showed better recovery than when training was only supported by continuous stimulation (Bonizzato et al. 2018). This concept of brain spine-interface was validated in non-human primates (Capogrosso et al. 2016). Clinatec (Grenoble, France) has developed a fully implantable electrocorticogram (ECoG) recording device with a 64-channel epidural electrode array capable of recording electrical signals from the motor cortex for an extended period of time and with a high signal to noise ratio the electrical signals from the motor cortex. This ECoG-based system allowed tetraplegic patients to control an exoskeleton (ClinicalTrials.gov, NCT02550522) with up to 8 degrees of freedom for the upper limb control (Benabid et al. 2019). This device was implanted in 2 individuals so far; one of them has been using this system both at the hospital and at home for more than 3 years. We hypothesize that ECoG-controlled EES in individuals with SCI will establish a direct bridge between the patient's motor intention and the spinal cord below the lesion, which will not only improve or restore voluntary control of leg movements, but will also boost neuroplasticity and neurological recovery when combined with neurorehabilitation.

Official Title
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Brain-controlled Spinal Cord Stimulation in Patients With Spinal Cord Injury

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: STIMO-BSI system implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having completed the main phase of the STIMO study (NCT02936453). SCI graded as American Spinal Injury Association Impairment Scale (AIS) A, B, C & D Level of lesion: T10 and above, based on AIS level determination by the PI, with preservation of conus function The intact distance between the cone and the lesion must be at least 60 mm. Focal spinal cord disorder caused by either trauma or epidural, subdural or intramedullary bleeding Minimum 12 months post-injury Completed in-patient rehabilitation program Stable medical, physical and psychological condition as considered by Investigators Able to understand and interact with the study team in French or English Adequate care-giver support and access to appropriate medical care in patient's home community Must agree to comply in good faith with all conditions of the study and to attend all required study training and visit Must provide and sign the Informed Consent prior to any study related procedures Exclusion Criteria: Limitation of walking function based on accompanying (CNS) disorders (systemic malignant disorders, cardiovascular disorders restricting physical training, peripheral nerve disorders) History of severe autonomic dysreflexia Brain damage Epilepsy Spinal stenosis Use of an intrathecal Baclofen pump. Any active implanted cardiac device such as pacemaker or defibrillator. Any indication that would require diathermy. Any indication that would require MRI. Increased risk for defibrillation. Severe joint contractures disabling or restricting lower limb movements. Haematological disorders with increased risk for surgical interventions (increased risk of haemorrhagic events). Congenital or acquired lower limb abnormalities (affection of joints and bone). Women who are pregnant (pregnancy test obligatory for women of childbearing potential) or breast feeding or not willing to take contraception. Known or suspected non-compliance, drug or alcohol abuse. Spinal cord lesion due to either a neurodegenerative disease or a tumor. Gastrointestinal ulcers in the last five years Known or suspected eye disorders or diseases Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.) Any other anatomic or co-morbid conditions that, in the investigator's opinion, could limit the patient's ability to participate in the study or to comply with follow-up requirements, or impact the scientific soundness of the study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All participants<br>All participants receive the same intervention. | Device: STIMO-BSI system implantation<br>* Participants are implanted bilaterally with epidural electrocorticography devices. The decoded motor intentions are driving the implanted spinal cord stimulation system. Brain-controlled spinal cord stimulation is used for training and rehabilitation to recover voluntary movements.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Measure | Number of Adverse Events possibly, probably or causally related to the procedure or device. | Through study completion, an average of 1 year | 
| Safety Measure | Number of device deficiencies | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WISCI II score | From 0 to 20, higher scores mean a better outcome | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| 10mWT |  | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| Weight bearing capacity |  | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| SCIM III score | From 0 to 100, higher scores mean a better outcome | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| 6minWT |  | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| Time Up and Go |  | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| Maximum Voluntary Contraction |  | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| ASIA score | From 0 to 100, higher scores mean a better outcome | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| Modified Ashworth Scale | From 0 to 4, higher scores mean a worst outcome | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| Berg Balance Scale | From 0 to 56, higher scores mean a better outcome | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| Gait Analysis | Average step height, step length, amplitude of EMG activity during walking | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| WHOQOL-BREF | From 0 to 100, higher scores mean a better outcome | 1 week before implantation, 8 weeks and 19 weeks after implantation | 
| BCI performance measures | Decoding accuracy from 0-100% higher numbers mean a better outome | 8 weeks and 19 weeks after implantation | 
| Upper Limb Neurobiomechanics | Average range of movement, amplitude of EMG activity during upper limb movements | 8 weeks and 19 weeks after implantation | 
| ECoG signal stability | Power density spectrum of the ECoG signal over each electrode | 8 weeks and 19 weeks after implantation | 
| SSEP | Amplitude and latency of the cortically evoked potentials | 8 weeks and 19 weeks after implantation |