Rebuilding Inter-limb Transfer in Cervical SCI

Early Phase 1

Recruiting

• Conditions: Cervical Spinal Cord Injury
• Interventions: Device: PCMS + Contralateral Motor Training; Device: PCMS + Rest; Device: Sham PCMS + Contralateral Motor Training

• Registration Number: NCT06440538
• Lead Sponsor: The Cleveland Clinic

Brief Summary

The purpose of this study in people living with cervical Spinal Cord Injury (SCI) is to examine the effects of paired neurostimulation (i.e., PCMS) combined with contralateral motor training on inter-limb transfer of ballistic motor and hand dexterity skills.

Detailed Description

Cervical spinal cord injury (SCI) is the most common and severe type of SCI that can lead to paralysis of the trunk and all four limbs, also known as tetraplegia. People with tetraplegia place a high priority on regaining upper limb motor function to be independent in daily life. Despite intensive therapies, upper limb motor gains are slow to emerge, especially in chronic cases.

A critical barrier to effective and efficient upper limb rehabilitation in cervical SCI lies in the motor deficits of inter-limb transfer. Inter-limb transfer refers to a natural innate process within the human neuromotor system that motor skills acquired in one limb can transfer to the opposite, untrained limb, and is believed to play a key role in maximizing and accelerating post-injury recovery. Inter-limb transfer however is deficient following cervical SCI due to a breakdown of inter-limb neural connections at the cortical and spinal levels. Prior studies in uninjured people reveal that one can upregulate inter-limb neural mechanisms and hence augment inter-limb transfer effects by giving neurostimulation to augment corticomotoneuronal pathways to the untrained arm just before motor training in the contralateral arm.

This study aims to rebuild inter-limb transfer of motor gains in chronic cervical SCI using a novel non-invasive neurostimulation method called paired corticospinal-motor neuronal stimulation (PCMS). We will test the central hypothesis that PCMS given to an untrained hand immediately before the visuomotor ballistic motor training at the other hand will improve inter-limb transfer of ballistic motor and dexterity skills to the untrained hand, based on potentiation of inter-limb neural mechanisms.

Study Timeline

• Study First Submitted: 2023-10-10
• Study Start: 2024-02-15
• Study First Submitted QC: 2024-06-03
• Study First Posted: 2024-06-04
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-11
• Last Update Posted: 2024-10-15
• Primary Completion: 2025-07-30
• Study Completion: 2025-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• Neurological Level of Injury C4, C5, C6, C7, C8
• American Spinal Injury Association Impairment Scale (AIS) C-D
• greater than or equal to 1 year time post injury
• residual motor sparing of bilateral FDI muscles, defined as medical research council (MRC) grade 2 to 5

Exclusion Criteria

• contraindications to transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) including pacemaker, metal in the skull, seizure history, pregnancy, etc.
• history of alcohol and/or drug abuse
• current usage of medications that can potentially lower the seizure threshold such as bupropion, amphetamines, etc.
• history of other neurological conditions such as stroke, Parkinson's, and traumatic brain injury (TBI)
• active pressure ulcers to avoid disruption of ongoing medical treatments
• participation of on-going upper-limb therapies to minimize confounding effects
• excessive tone/spasticity (Modified Ashworth Scale [MAS] >3) and severe contractures or soft tissue shortening at elbow/wrist/fingers

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
PCMS + Contralateral Motor Training	PCMS + Contralateral Motor Training	-
PCMS + Rest	PCMS + Rest	-
Sham PCMS + Contralateral Motor Training	Sham PCMS + Contralateral Motor Training	-

Primary Outcome Measures

Name	Time	Method
Change in excitability of cortical and corticospinal physiology and interhemispheric connections (TMS)	Baseline to post paired TMS and PNS stimulation, assessed for approximately 4-6 hours	Transcranial magnetic stimulation will be used to test cortical output from both hemispheres and will be measured as motor evoked potentials(MEPS) of the First Dorsal Interosseous (FDI) muscle.
Change in ballistic acceleration	Baseline to post paired TMS and PNS stimulation, assessed for approximately 4-6 hours	Participants perform 10 trials of ballistic index finger abduction with a accelerometer attached to index finger to capture the peak acceleration during the movement.
Change in excitability of spinal physiology (F-wave)	Baseline to post paired TMS and PNS stimulation, assessed for approximately 4-6 hours	Peripheral Nerve stimulation will be performed to collect the spinal F-wave amplitude of the First Dorsal Interosseous (FDI) muscle.

Secondary Outcome Measures

Name	Time	Method
Change in finger velocity smoothness during NHPT	Baseline to post paired TMS and PNS stimulation, assessed for approximately 4-6 hours	The investigator will calculate the index finger(2nd digit) velocity smoothness using the number of local maxima of frontal plane finger velocities during the peg transfer phase using kinematic sensors place on the fingers.
Change in Nine Hole Peg Test (NHPT)	Baseline to post paired TMS and PNS stimulation, assessed for approximately 4-6 hours	The NHPT is used to measure finger dexterity measured in time to complete the test or amount of pegs placed in 100 sec.

Trial Locations

Locations (1)

Lerner Research Institute; Cleveland Clinid Foundation; 🇺🇸 Cleveland, Ohio, United States