NIBS Therapy in Subacute Spinal Cord Injury

Tetraplegia/Tetraparesis Clinical Trial

— NIBS-SCI1  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06247904
• Other study ID #: iRISID-2023-2494
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 15, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: Albert Einstein Healthcare Network
• Contact: Sapna Kumar, MSE
• Phone: 215-663-6227
• Email: sapna.kumar[@]jefferson.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Post 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-C

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.

Related Conditions & MeSH terms

• Quadriplegia
• Spinal Cord Injuries
• Tetraplegia/Tetraparesis
• Traumatic Spinal Cord Injury
• Wounds and Injuries

Intervention

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.
• 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

Locations

Country	Name	City	State
United States	Jefferson Moss-Magee Rehabilitation - Elkins Park	Elkins Park	Pennsylvania

Sponsors (7)

Lead Sponsor	Collaborator
Albert Einstein Healthcare Network	Burke Medical Research Institute, Massachusetts General Hospital, Pennsylvania Department of Health, University of Mississippi Medical Center, University of Sao Paulo, Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Recruitment - (Percentage candidates enrolled of approached patients)	The proportion of eligible patients who agree to take part in the study.	21 months (Recruitment period)
Primary	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)
Primary	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)
Primary	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)
Primary	Adverse Events	Rate of adverse and serious adverse events	2 years (Duration of human subjects' involvement)
Secondary	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
Secondary	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
Secondary	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