NIBS Therapy in Subacute Spinal Cord Injury (NIBS-SCI1)

Albert Einstein Healthcare Network

Status: Invitation-only

Conditions: Traumatic Spinal Cord Injury; Tetraplegia/Tetraparesis

Treatments: Device: Active rTMS; Device: sham rTMS

Study type: Interventional

Funder types: Other

Identifiers

NCT06247904

iRISID-2023-2494

Details and patient eligibility

About

No accepted clinical therapies exist for repair of motor pathways following spinal cord injury (SCI) in humans, leaving permanent disability and devastating personal and socioeconomic cost. A robust neural repair strategy has been demonstrated in preclinical studies, that is ready for translation to recovery of hand and arm function in human SCI, comprising daily transcranial magnetic stimulation treatment at the inpatient rehabilitation facility. This study will establish clinical effect size of the intervention, as well as safety and feasibility necessary for a subsequent controlled efficacy trial and inform preclinical studies for dosing optimization.

Full description

The objective of this proposal is to begin translating findings from pre-clinical studies to human motor deficits following cervical SCI (cervSCI). This HF-rTMS treatment protocol has not been previously assessed in human SCI and is qualitatively different from rTMS protocols reported to transiently modulate excitability of existing pathways, previously demonstrated in the literature. The protocol involves a daily stimulation of ~10 mins bilateral HF-rTMS for 2 weeks. SCI participants will be studied in a United States inpatient setting for this phase I study.

Given the findings in the pre-clinical model of robust axonal sprouting and functional synapse formation close to the damaged tissue using the above stimulation parameters, the transcranial magnetic stimulation treatment will target the hand-forearm region of the primary motor cortex, bilaterally. The aim is to include the cortical representation of affected muscles adjacent to the neurological level of injury. This zone often contains a mix of clinically and neurophysiologically intact, weakly innervated and denervated corticospinal pathways. Under standard sub-acute rehabilitation care, recovery of up to 1 neurological level of injury (NLI) is often the case, but improvement of 2 or more levels is far less common (<30% of patients). To examine the feasibility and safety of this novel intervention is the principal aim of the study. The associated potential clinical and neurophysiological changes will also be evaluated. These preliminary data will be used to power a subsequent efficacy trial to test the hypothesis that rTMS induced corticospinal augmentation will result in greater than typical extension of the NLI in human SCI, assessed up to the stable recovery phase at 6 months post-injury.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Post traumatic or non-traumatic cervical spinal cord injury (SCI) with residual upper-extremity paralysis
2. Time post-injury less than six weeks
3. Neurological Level of Injury (NLI) C4-C6
4. ASIA Impairment Scale (AIS) A-D
5. Sensory and motor zone of partial preservation (ZPP, clinically complete or incomplete)
6. Age 18 to 80 years old

Exclusion criteria

1. Ventilator dependence;
2. Concurrent neurological condition affecting sensory or motor pathways or otherwise limiting ability to participate in the study;
3. Evidence of trauma-related brain injury;
4. Contraindications for TMS or history of seizure or seizure risk;
5. Spinal instability;
6. Uncontrolled autonomic dysreflexia;
7. Severe muscular or skeletal or neuropathic pain;
8. Known or suspected pregnancy;
9. Medically unstable or any reason the physician may deem as inappropriate for the participant to enroll or continue in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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20 participants in 2 patient groups

Active rTMS

Active Comparator group

Description:

10 daily sessions of High-frequency Transcranial Magnetic Stimulation (HF-rTMS) applied bilaterally over the hand primary motor area informed by e-field modelling and targeting will be aided by neuronavigation system for precise targeting during each intervention session. Active group will receive HF-rTMS intensity calculated using electric field modelling to create electric field intensity of approximately motor threshold, using the cool-B65 A/P rTMS coil.

Treatment:

Device: Active rTMS

Sham rTMS

Sham Comparator group

Description:

10 daily sessions of Sham High-frequency Transcranial Magnetic Stimulation (HF-rTMS) applied bilaterally over the hand primary motor area informed by e-field modelling and targeting will be aided by neuronavigational system for precise targeting during each intervention session Sham group receives no active magnetic stimulation. Cool-B65 A/P rTMS coil will be used to avoid unblinding of administrator and/or study participant.

Treatment:

Device: sham rTMS