Brain-controlled Spinal Cord Stimulation in Patients With Spinal Cord Injury (STIMO-BSI)

• ClinicalTrials.gov Identifier: NCT04632290
• Recruitment Status: Unknown
• First Posted: November 17, 2020
• Last Update Posted: November 5, 2021
• Sponsor: Ecole Polytechnique Fédérale de Lausanne
• Information provided by (Responsible Party): Jocelyne Bloch, Centre Hospitalier Universitaire Vaudois

Tracking Information

• First Submitted Date: November 5, 2020
• First Posted Date: November 17, 2020
• Last Update Posted Date: November 5, 2021
• Actual Study Start Date: July 4, 2021
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 11, 2020)

• Safety Measure [ Time Frame: Through study completion, an average of 1 year ]
  Number of Adverse Events possibly, probably or causally related to the procedure or device.
• Safety Measure [ Time Frame: Through study completion, an average of 1 year ]
  Number of device deficiencies

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 17, 2020)

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

Original Secondary Outcome Measures (submitted: November 11, 2020)

• WISCI II score [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• 10mWT [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• Weight bearing capacity [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• SCIM III score [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• 6minWT [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• Time Up and Go [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• Maximum Voluntary Contraction [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• ASIA score [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• Modified Ashworth Scale [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• Berg Balance Scale [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• Gait Analysis [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• WHOQOL-BREF [ Time Frame: 1 week before implantation, 8 weeks and 19 weeks after implantation ]
• BCI performance measures [ Time Frame: 8 weeks and 19 weeks after implantation ]
• Upper Limb Neurobiomechanics [ Time Frame: 8 weeks and 19 weeks after implantation ]
• ECoG signal stability [ Time Frame: 8 weeks and 19 weeks after implantation ]
• SSEP [ Time Frame: 8 weeks and 19 weeks after implantation ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Spinal Cord Injuries

Intervention

Device: STIMO-BSI system implantation

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.

Study Arms

Experimental: All participants

All participants receive the same intervention.

Intervention: Device: STIMO-BSI system implantation

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 11, 2020): 3
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2023
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT04632290
• Other Study ID Numbers: STIMO-BSI
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jocelyne Bloch, Centre Hospitalier Universitaire Vaudois
• Original Responsible Party: Same as current
• Current Study Sponsor: Ecole Polytechnique Fédérale de Lausanne
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jocelyne Bloch; Centre Hospitalier Universitaire Vaudois

• PRS Account: Ecole Polytechnique Fédérale de Lausanne
• Verification Date: November 2021