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

Noninvasive Brain Stimulation Therapy in Subacute Human Spinal Cord Injury: A Translational Study

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Traumatic Spinal Cord Injury; Tetraplegia/Tetraparesis
• Intervention / Treatment: Device: Active rTMS; Device: sham rTMS

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Elkins Park, Pennsylvania, United States, 19027
      • Jefferson Moss-Magee Rehabilitation - Elkins Park

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active rTMS; 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.	Device: Active rTMS; The stimulation protocol will comprise 15Hz pulse trains, each 50 pulses, repeated 10x, with a 60s inter-train interval. Stimulation intensity will be determined from individual MRI-modeled e-field, to achieve approximately motor threshold in the target area.; Other Names: active repetitive transcranial magnetic stimulation
Sham Comparator: Sham rTMS; 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.	Device: sham rTMS; The stimulation protocol will comprise 15Hz pulse trains, each 50 pulses, repeated 10x, with a 60s inter-train interval. Stimulation intensity will be close to zero (negligible) since sham coil will be used for the intervention; Other Names: sham repetitive transcranial magnetic stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eligibility - (Percentage candidates eligible of screened patients)	The proportion of patients who can take part in the study, whether they later agree to or not.	21 months (Recruitment period)
Recruitment - (Percentage candidates enrolled of approached patients)	The proportion of eligible patients who agree to take part in the study.	21 months (Recruitment period)
Adherence to intervention - (Percentage candidates who dropout during the intervention period of enrolled candidates)	Proportion of intervention-related dropouts.	2 years (Duration of human subjects' involvement)
Adherence to outcome assessment - (Percentage candidates who do not complete outcome assessments of enrolled candidates)	Proportion of patients that complete the assessments at the start and the end of the intervention.	2 years (Duration of human subjects' involvement)
Retention - (Percentage candidates who do not complete 6-month follow up of enrolled candidates)	The number of patients who drop out or were 'lost' at the 6-month follow-up.	2 years (Duration of human subjects' involvement)
Adverse Events	Rate of adverse and serious adverse events	2 years (Duration of human subjects' involvement)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor neurological level change (ISNCSCI assessment)	Proportion of patients with Improvement of 2 or more motor zone of partial preservation levels from baseline to 6 months after injury.	Baseline and 6 months after injury
Incidence of reconnectivity (Proportion: MEP absent, covert to MEP present)	The proportion of re-connectivity will be estimated by treatment group.	Baseline and 6 months after injury
Change in motor threshold between groups (Difference in %Maximum Stimulator Output to achieve motor threshold)	Change in motor threshold of key muscles will be estimated bilaterally within each group and a comparison of the change between groups.	Baseline and 6 months after injury

Collaborators and Investigators

• Sponsor: Albert Einstein Healthcare Network
• Collaborators: Massachusetts General Hospital; Weill Medical College of Cornell University; University of Sao Paulo; Pennsylvania Department of Health; University of Mississippi Medical Center; Burke Medical Research Institute
• Investigators: Principal Investigator: Dylan J Edwards, PhD, Albert Einstein Healthcare Network

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: January 31, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Recovery; Transcranial Magnetic Stimulation; Spinal cord injury; Motor cortex; Cervical spinal cord
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Paralysis; Wounds and Injuries; Spinal Cord Injuries; Quadriplegia
• Other Study ID Numbers: iRISID-2023-2494

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon completion of the study, data will be deidentified and shared within the supplementary material of published scientific papers or per the journal recommendations. We may also share the full range of available individual participant data with the members of the scientific community upon reasonable request and at the discretion of the PI.
• IPD Sharing Time Frame: Data will become available upon publication of results and may be shared indefinitely.
• IPD Sharing Access Criteria: IPD and any additional supporting information will be shared with members of the scientific and medical communities for analyses related to the use of rTMS to improve upper extremity motor function following neurological insult. The mechanism for data sharing will be decided on a case by case basis; the study PI will review all data sharing request.
• IPD Sharing Supporting Information Type: SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No