Clinical trial NCT04632290: Brain-controlled Spinal Cord Stimulation in Patients With Spinal Cord Injury
Official title: Brain-controlled Spinal Cord Stimulation in Patients With Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spinal Cord Injuries
Lead sponsor: Ecole Polytechnique Fédérale de Lausanne
Sponsor class: OTHER
First posted: 2020-11-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety Measure
timeFrame: Through study completion, an average of 1 year
measure: Safety Measure
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: WISCI II score
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: 10mWT
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: Weight bearing capacity
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: SCIM III score
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: 6minWT
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: Time Up and Go
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: Maximum Voluntary Contraction
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: ASIA score
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: Modified Ashworth Scale
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: Berg Balance Scale
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: Gait Analysis
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: WHOQOL-BREF
timeFrame: 1 week before implantation, 8 weeks and 19 weeks after implantation
measure: BCI performance measures
timeFrame: 8 weeks and 19 weeks after implantation
measure: Upper Limb Neurobiomechanics
timeFrame: 8 weeks and 19 weeks after implantation
measure: ECoG signal stability
timeFrame: 8 weeks and 19 weeks after implantation
measure: SSEP
timeFrame: 8 weeks and 19 weeks after implantation
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: CHUV
state: Vaud
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Jocelyne Bloch
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seanez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71. doi: 10.1038/s41586-018-0649-2. Epub 2018 Oct 31.
citation: Capogrosso M, Milekovic T, Borton D, Wagner F, Moraud EM, Mignardot JB, Buse N, Gandar J, Barraud Q, Xing D, Rey E, Duis S, Jianzhong Y, Ko WK, Li Q, Detemple P, Denison T, Micera S, Bezard E, Bloch J, Courtine G. A brain-spine interface alleviating gait deficits after spinal cord injury in primates. Nature. 2016 Nov 10;539(7628):284-288. doi: 10.1038/nature20118.
citation: Benabid AL, Costecalde T, Eliseyev A, Charvet G, Verney A, Karakas S, Foerster M, Lambert A, Moriniere B, Abroug N, Schaeffer MC, Moly A, Sauter-Starace F, Ratel D, Moro C, Torres-Martinez N, Langar L, Oddoux M, Polosan M, Pezzani S, Auboiroux V, Aksenova T, Mestais C, Chabardes S. An exoskeleton controlled by an epidural wireless brain-machine interface in a tetraplegic patient: a proof-of-concept demonstration. Lancet Neurol. 2019 Dec;18(12):1112-1122. doi: 10.1016/S1474-4422(19)30321-7. Epub 2019 Oct 3.
citation: Bonizzato M, Pidpruzhnykova G, DiGiovanna J, Shkorbatova P, Pavlova N, Micera S, Courtine G. Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury. Nat Commun. 2018 Aug 1;9(1):3015. doi: 10.1038/s41467-018-05282-6.