Brain-controlled Spinal Cord Stimulation in Participants With Chronic Stroke for Lower and Upper Limb Rehabilitation

Обзор

The purpose of this clinical study is to evaluate the preliminary safety and effectiveness of using a cortical recording device (ECoG) combined with cervical and lumbar targeted epidural electrical stimulation (EES) of the spinal cord to restore voluntary motor functions of upper and lower limbs in participants with chronic stroke suffering from mobility impairment. The goal is to establish a direct bridge between the motor intention of the participant and the spinal cord, which should not only improve or restore voluntary control of arm and leg movement and support immediate mobility, but also promote neurological recovery when combined with neurorehabilitation.

Подробное описание

In a current first-in-human clinical trial, called STIMO (ClinicalTrials.gov, NCT02936453), Electrical Epidural 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, EES immediately enhances walking function and, with repeated use as part of the EES-assisted neurorehabilitation program, improves leg motor control and neurological recovery in severe SCI participants to a certain extent. Linking brain activity to spinal stimulation, as shown in preclinical and clinical studies, enhances usability of EES and neurological recovery.

Clinatec (CEA, Grenoble, France) has developed an implantable electrocorticogram (ECoG) recording device with a 64-channel epidural electrode array called WIMAGINE capable of recording electrical signals from the motor cortex for an extended period and with a high signal to noise ratio. This ECoG-based system allowed tetraplegic patients to control an exoskeleton (Clinicaltrials.gov, NCT 02550522) with up to 8 degrees of freedom for the upper limb control. This device has been implanted in 5 chronic participants so far; one of them has been using this system both at the hospital and at home for more than 3 years.

The WIMAGINE ECoG technology has been integrated with epidural electrical stimulation (EES) across multiple clinical trials exploring implantable brain-spine interfaces. In the STIMO-BSI trial (NCT04632290), real-time decoding of cortical motor intentions for leg movements was used to modulate lumbar EES, enabling a chronic SCI participant to regain volitional control of standing and walking, with neurological improvements persisting even without the system after three years. In the UP2 trial (NCT05665998), two participants with incomplete C3/C4 SCI received cervical EES arrays and a WIMAGINE implant to decode up to six upper-limb motor states; brain-controlled cervical EES was shown to be safe, feasible, and supportive of neurological recovery of arm and hand function. In the Think2Go trial (NCT06243952), two participants with complete motor paraplegia received a WIMAGINE implant paired with the ARC-IM lumbar EES system, enabling lower-limb movement within days and leading to restored voluntary leg control and unsupported walking after months of rehabilitation. Together, these studies demonstrate that implantable ECoG-based brain-spine interfaces can safely decode motor intentions and drive targeted EES to restore multi-limb motor functions and promote neurological recovery across a range of SCI severities.

In this study, the investigators will assess the preliminary safety and effectiveness of ECoG-controlled EES in individuals with chronic stroke who suffer from hemiplegia, to establish a direct bridge between the motor intention and the spinal cord. This could improve or restore voluntary control of arm and leg movement as well as promote neurological recovery when combined with neurorehabilitation. The WIMAGINE ECoG system will be coupled with the ARC-IM purpose-built spinal cord stimulation technology in the ARC-BSI Stroke system, which is equivalent technology to systems currently used in the UP2 (ARC-BSI Cervical system) and Think2Go (ARC-BSI Lumbar system) clinical studies.

Вмешательства

• Устройство ARC-BSI Stroke system
  Implantation of a 64 channel - ECoG array over the sensory motor cortex of one side's upper and lower limbs, combined with an implantation of two 16 channel spinal cord stimulation system, one over the cervical region and one over the lumbar region. 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.

Первичные конечные точки

• Preliminary safety [Срок оценки: From enrollment until End of the Study timepoint (at 5 years)]

Вторичные конечные точки (12)

• Fugl-Meyer Assessment Lower Extremities [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• 10 Meters Walk Test (10MWT) [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• 6 Minute Walk Test (6MWT): [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• Timed Up and Go (TUG): [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• EMG-based Gait Analysis [Срок оценки: Baseline, 6-Months measures, 1-Year Measures, then Yearly Measures until 5 years.]
• Kinematics-based Gait Analysis [Срок оценки: Baseline, 6-Months measures, 1-Year Measures, then Yearly Measures until 5 years.]
• Fugl-Meyer Assessment Upper Extremities (FMA-UE) [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• Action Research Arm Test (ARAT) [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• Box and Block Test (BBT) [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• Range of Motion [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• Modified Ashworth Scale (MAS) [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]
• Chedoke-McMaster Stroke Assessment (CMSA) [Срок оценки: Pre-implantation: Baseline (B) Post-implantation (counting from first surgery) :6-Months measures (M6), 1-Year Measures (Y1), then Yearly Measures until 5 years (Y2, Y3, Y4 and Y5). All the timepoint Measures last 1 to 2 weeks.]

Критерии участия

Критерии включения

• Must be between 18-70 years old at the time of enrolment.
• Must have suffered from a subcortical including brain stem stroke that occurred at least 9 months but not more than 10 years prior to enrolment.
• Must have a score lower than 25 on the Fugl-Meyer upper-limb scale.
• Must be able to stand with or without assistive device for 30 seconds.
• Must have a score higher than 22 at the Montreal Cognitive Assessment.
• Must present right or left hemiplegia.
• Must have completed primary standard of care rehabilitation.
• Must provide and sign the study's Informed Consent prior to any study-related procedures.
• Must be able to understand and interact with the study team in French or English.
• Must agree to comply in good faith with all conditions of the study and to attend all scheduled appointments.
• Must use effective contraception for women of childbearing capacity.
• Must be able to withhold antiplatelet/anticoagulation agents perioperatively for the time of the surgeries (if applicable).

Критерии исключения

• Must not be pregnant or breast feeding (if applicable).
• Must not have the intention to become pregnant during the study (if applicable).
• Must not have any diseases and conditions that would increase the morbidity and mortality of the implantation surgery.
• Must not have any mental instability, including a diagnosis of personality disorder, psychosis, substance abuse, or severe depression as assessed by the psychologist.
• Must not have any other medical conditions that would make the subject unable to participate in testing in the judgment of the investigators (e.g., major cognitive disorder, renal failure, hepatic dysfunction, epilepsy, etc.).
• Must not have ongoing significant dysphagia or aspiration difficulties or require ventilator support.
• Must not have any active implanted device, such as a pacemaker or other neurostimulator.
• Must not have any spinal anatomical abnormalities or incompatibilities with the implanted system precluding surgery.
• Must not have severe spasticity of the upper limb or lower limb (Modified Ashworth Scale > 3).
• Must not have indication requiring frequent MRIs.
• Must not participate in another clinical study using drugs or medical devices that might interfere with the outcomes of the study.
• Must not be the investigator him/herself, his/her family members, employees, and other dependent persons.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Швейцария · 1 центр

• Centre Hospitalier Universitaire Vaudois (CHUV) — Lausanne

Публикации

• Ajiboye AB, Willett FR, Young DR, Memberg WD, Murphy BA, Miller JP, Walter BL, Sweet JA, Hoyen HA, Keith MW, Peckham PH, Simeral JD, Donoghue JP, Hochberg LR, Kirsch RF. Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration. Lancet. 2017 May 6;389(10081):1821-1830. doi: 10.1016/S0140-6736(17)30601-3 PMID 28363483
• Hochberg LR, Bacher D, Jarosiewicz B, Masse NY, Simeral JD, Vogel J, Haddadin S, Liu J, Cash SS, van der Smagt P, Donoghue JP. Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature. 2012 May 16;485(7398):372-5. doi: 10.1038/nature11076. PMID 22596161
• Jovanovic LI, Kapadia N, Zivanovic V, Rademeyer HJ, Alavinia M, McGillivray C, Kalsi-Ryan S, Popovic MR, Marquez-Chin C. Brain-computer interface-triggered functional electrical stimulation therapy for rehabilitation of reaching and grasping after spinal cord injury: a feasibility study. Spinal Cord Ser Cases. 2021 Mar 19;7(1):24. doi: 10.1038/s41394-020-00380-4. PMID 33741900
• Schirmer CM, Shils JL, Arle JE, Cosgrove GR, Dempsey PK, Tarlov E, Kim S, Martin CJ, Feltz C, Moul M, Magge S. Heuristic map of myotomal innervation in humans using direct intraoperative nerve root stimulation. J Neurosurg Spine. 2011 Jul;15(1):64-70. doi: 10.3171/2011.2.SPINE1068. Epub 2011 Apr 8. PMID 21476796
• Uchiyama S, Ishizuka N, Shimada K, Teramoto T, Yamazaki T, Oikawa S, Sugawara M, Ando K, Murata M, Yokoyama K, Minematsu K, Matsumoto M, Ikeda Y; JPPP Study Group. Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors: Japanese Primary Prevention Project. Stroke. 2016 Jun;47(6):1605-11. doi: 10.1161/STROKEAHA.115.012461. Epub 2016 May 10. PMID 27165949
• Puentes S, Kaido T, Hanakawa T, Ichinohe N, Otsuki T, Seki K. Internal capsule stroke in the common marmoset. Neuroscience. 2015 Jan 22;284:400-411. doi: 10.1016/j.neuroscience.2014.10.015. Epub 2014 Oct 20. PMID 25453768
• Kato K, Sawada M, Nishimura Y. Bypassing stroke-damaged neural pathways via a neural interface induces targeted cortical adaptation. Nat Commun. 2019 Oct 16;10(1):4699. doi: 10.1038/s41467-019-12647-y. PMID 31619680
• Lorach H, Galvez A, Spagnolo V, Martel F, Karakas S, Intering N, Vat M, Faivre O, Harte C, Komi S, Ravier J, Collin T, Coquoz L, Sakr I, Baaklini E, Hernandez-Charpak SD, Dumont G, Buschman R, Buse N, Denison T, van Nes I, Asboth L, Watrin A, Struber L, Sauter-Starace F, Langar L, Auboiroux V, Carda S, Chabardes S, Aksenova T, Demesmaeker R, Charvet G, Bloch J, Courtine G. Walking naturally after PMID 37225984

Идентификаторы

NCT: NCT07610850 · Stroke-BSI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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