Clinical trial NCT06698224: Paired Spinal Cord and Peripheral Nerve Stimulation to Recover Hand Function in SCI
Official title: Paired Spinal Cord and Peripheral Nerve Stimulation for Hand Function Recovery in Humans Post Cervical SCI
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Spinal Cord Injury
Spinal Cord Disease
Spinal Cord Injuries (SCI)
Keywords: Spinal cord injury
Hand function
Spinal cord stimulation
Paired stimulation
Physical therapy
Lead sponsor: Kessler Foundation
Sponsor class: OTHER
First posted: 2024-11-20
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: For SCI participants:

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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:

Inclusion Criteria:

* At least 18 years of age

Exclusion Criteria:

* 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)

Primary outcomes:
measure: GRASSP
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: NRS
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Voluntary hand opening and closing kinematics
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Maximal voluntary grip strength
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Transcranial magnetic stimulation motor evoked potential (MEP)
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: F-wave
timeFrame: From enrollment to the end of treatment at 4 weeks
Secondary outcomes:
measure: Functional Neurophysiological assessment (FNPA)
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Multisegmental Motor Response (MMR)
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Capabilities of Upper Extremity Questionnaire (CUE-Q)
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Spinal Cord Injury-Quality of Life (SCI-QOL) Questionnaire
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) - ASIA Impairment Scale (AIS)
timeFrame: From enrollment to the end of treatment at 4 weeks
Other outcomes:
Locations:
city: West Orange
country: United States
facility: Kessler Foundation
state: New Jersey
Study officials:
affiliation: Kessler Foundation
name: Gail Forrest, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.