Paired Spinal Cord and Peripheral Nerve Stimulation to Recover Hand Function in SCI

Официальное название

Paired Spinal Cord and Peripheral Nerve Stimulation for Hand Function Recovery in Humans Post Cervical SCI

Обзор

Individuals who suffer a spinal cord injury in the neck region have difficulty using their hands due to paralysis and/or weakness of their arms and hand muscles. This project aims to test the effects of pairing spinal cord and nerve stimulation combined with physical therapy training in recovering arms and hand function. The long-term goal is to provide better therapies that will improve the ability of individuals with spinal cord injuries to use their arms and hands to perform everyday tasks, similar to injury before.

Подробное описание

Cervical spinal cord injury (SCI) results in paralysis and/or weakness of arms and hands that severely affects the independence and quality of life post-injury. Therefore, regaining arm and hand function remains the top priority of this population. Considering that SCI is mostly incomplete in nature, recent evidence suggests that physical or occupational therapy training combined with spinal cord transcutaneous stimulation (scTS) is effective in restoring arm and hand function post-cervical SCI. scTS is a non-invasive painless technique that augments the intrinsic capacity of the spinal cord to facilitate motor function post-SCI. The beneficial effects of scTS can be further improved by coupling it with peripheral nerve stimulation (PNS), which supplies the arm and hand muscles.

This study aims to investigate how precisely timed paired application of spinal cord transcutaneous stimulation (scTS) and peripheral nerve stimulation (PNS) combined with physical therapy can improve the use of arms and hands in those with a SCI. Spinal cord transcutaneous stimulation (scTS) is a non-invasive electrical stimulation provided on top of the skin over specific areas of the spinal cord to excite the nervous system for the activity being trained and promote connections between the brain and spinal cord. Peripheral nerve stimulation (PNS) is a non-invasive electrical stimulation provided on top of the skin over specific areas of the arm, forearm, and hand to excite the peripheral nerves and promote connections between the spinal cord and the muscles involved in the activity-based recovery training. We hypothesize that precisely timed application of scTS and PNS will increase spinal cord excitability. Increased spinal cord excitability coupled with physical therapy will facilitate hand function recovery post-SCI.

Study aims:

1. To establish optimal time sequencing for the paired scTS and PNS delivery resulting in the spinal cord motor neuron excitability in non-injured (NI) and SCI participants. 2. To investigate the acute effects of paired scTS and PNS delivery on spinal cord motor neuron and corticospinal excitability. 3. To investigate the effectiveness of paired scTS and PNS along with scTS combined with AB-UET in recovering hand function post cervical SCI. 4. To identify the potential mechanisms of action underlying the observed changes in the hand function following training with paired scTS and PNS along with scTS combined with AB-UET.

This is a pretest-posttest experimental design. SCI participants will be enrolled for Aims 1, 2, 3 and 4. For SCI participants, On site medical evaluation, ASIA Impairment Scale (ISNCSCI-AIS), MVC grip strength and nerve intactness study will be collected or performed during the screening process. If the individual is potentially eligible for the study, as determined by the study physician and investigators, they will undergo pre-training assessments, 20 training sessions, and post-training assessments. Non-Injured (NI) participants will be enrolled for Aims 1 and 2.

Вмешательства

• Устройство Spinal cord transcutaneous stimulation
  Physical therapy combined with spinal cord transcutaneous stimulation will increase activity in the paralyzed or weak arm and hand muscles in individuals with spinal cord injury. Transcutaneous spinal cord stimulation is a non-invasive stimulation strategy and are known to facilitate recovery of lost function post spinal cord injury.
• Устройство Paired spinal cord and peripheral nerve stimulation
  Physical therapy combined with paired spinal cord-peripheral nerve stimulation will increase activity in the paralyzed or weak arm and hand muscles in individuals with spinal cord injury. Transcutaneous spinal cord and peripheral nerve stimulation are both non-invasive stimulation strategy and are known to facilitate recovery of lost function post spinal cord injury.

Первичные конечные точки

• GRASSP [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• NRS [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• Voluntary hand opening and closing kinematics [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• Maximal voluntary grip strength [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• Transcranial magnetic stimulation motor evoked potential (MEP) [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• F-wave [Срок оценки: From enrollment to the end of treatment at 4 weeks]

Вторичные конечные точки (5)

• Functional Neurophysiological assessment (FNPA) [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• Multisegmental Motor Response (MMR) [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• Capabilities of Upper Extremity Questionnaire (CUE-Q) [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• Spinal Cord Injury-Quality of Life (SCI-QOL) Questionnaire [Срок оценки: From enrollment to the end of treatment at 4 weeks]
• International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) - ASIA Impairment Scale (AIS) [Срок оценки: From enrollment to the end of treatment at 4 weeks]

Критерии участия

For SCI participants:

Критерии включения

• At least 18 years of age
• Non-progressive cervical SCI
• Greater than or equal to 6-months post spinal cord injury
• Stable medical condition
• Viable median and ulnar nerve as evident from MMR and M-Wave recordings
• Wrist extensor and finger flexors score between 1-3 for both upper extremity for ISNCSCI motor assessment.

Критерии исключения

• Ventilator Dependent
• Untreated fracture or pressure ulcer
• Untreated psychiatric disorder or ongoing drug abuse
• Cardiac, respiratory, bladder, renal, or other untreated medical disorder unrelated to SCI
• Skeletal muscle Botox injections less than 6 months prior
• Previous tendon transfer of the arm or arms
• Any implanted pump (i.e., baclofen pump, pain pump, etc.) prior to randomization
• Pregnant at the time of enrollment or planning to become pregnant during the course of the study
• Unable or unwilling to wean from anti-spasticity medications
• History of seizure or epilepsy
• Metal in Head
• Cochlear implant
• Implanted brain stimulators
• Aneurysm clips
• Increased intracranial pressure (which lowers seizure threshold)
• Cardiac pacemaker
• Personal or family history of epilepsy
• Tricyclic antidepressants or neuroleptics (which lower seizure threshold)

For healthy volunteer/participants:

Критерии включения

• At least 18 years of age

Критерии исключения

• Neurological injury or disease
• Pregnant at the time of enrollment or planning to become pregnant during the course of the study
• Personal or family history of seizure or epilepsy
• Tricyclic antidepressants or neuroleptics (which lower seizure threshold)

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Kessler Foundation — West Orange

Публикации

• Sharma P, Naglah A, Aslan S, Khalifa F, El-Baz A, Harkema S, D'Amico J. Preservation of functional descending input to paralyzed upper extremity muscles in motor complete cervical spinal cord injury. Clin Neurophysiol. 2023 Jun;150:56-68. doi: 10.1016/j.clinph.2023.03.003. Epub 2023 Mar 17. PMID 37004296
• Singh G, Sharma P, Forrest G, Harkema S, Behrman A, Gerasimenko Y. Spinal Cord Transcutaneous Stimulation in Cervical Spinal Cord Injury: A Review Examining Upper Extremity Neuromotor Control, Recovery Mechanisms, and Future Directions. J Neurotrauma. 2024 Sep;41(17-18):2056-2074. doi: 10.1089/neu.2023.0438. Epub 2024 Jul 12. PMID 38874496
• Sharma P, Panta T, Ugiliweneza B, Bert RJ, Gerasimenko Y, Forrest G, Harkema S. Multi-Site Spinal Cord Transcutaneous Stimulation Facilitates Upper Limb Sensory and Motor Recovery in Severe Cervical Spinal Cord Injury: A Case Study. J Clin Med. 2023 Jun 30;12(13):4416. doi: 10.3390/jcm12134416. PMID 37445450
• Zhang F, Momeni K, Ramanujam A, Ravi M, Carnahan J, Kirshblum S, Forrest GF. Cervical Spinal Cord Transcutaneous Stimulation Improves Upper Extremity and Hand Function in People With Complete Tetraplegia: A Case Study. IEEE Trans Neural Syst Rehabil Eng. 2020 Dec;28(12):3167-3174. doi: 10.1109/TNSRE.2020.3048592. Epub 2021 Jan 28. PMID 33382659

Идентификаторы

NCT: NCT06698224 · 1176828

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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