Clinical trial NCT06247904: NIBS Therapy in Subacute Spinal Cord Injury
Official title: Noninvasive Brain Stimulation Therapy in Subacute Human Spinal Cord Injury: A Translational Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Traumatic Spinal Cord Injury
Tetraplegia/Tetraparesis
Keywords: Spinal cord injury
Cervical spinal cord
Transcranial Magnetic Stimulation
Recovery
Motor cortex
Lead sponsor: Albert Einstein Healthcare Network
Sponsor class: OTHER
Collaborators: name: Pennsylvania Department of Health
name: University of Mississippi Medical Center
name: University of Sao Paulo
name: Massachusetts General Hospital
name: Weill Medical College of Cornell University
name: Burke Medical Research Institute
First posted: 2024-02-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Eligibility - (Percentage candidates eligible of screened patients)
timeFrame: 21 months (Recruitment period)
measure: Recruitment - (Percentage candidates enrolled of approached patients)
timeFrame: 21 months (Recruitment period)
measure: Adherence to intervention - (Percentage candidates who dropout during the intervention period of enrolled candidates)
timeFrame: 2 years (Duration of human subjects' involvement)
measure: Adherence to outcome assessment - (Percentage candidates who do not complete outcome assessments of enrolled candidates)
timeFrame: 2 years (Duration of human subjects' involvement)
measure: Retention - (Percentage candidates who do not complete 6-month follow up of enrolled candidates)
timeFrame: 2 years (Duration of human subjects' involvement)
measure: Adverse Events
timeFrame: 2 years (Duration of human subjects' involvement)
Secondary outcomes:
measure: Motor neurological level change (ISNCSCI assessment)
timeFrame: Baseline and 6 months after injury
measure: Incidence of reconnectivity (Proportion: MEP absent, covert to MEP present)
timeFrame: Baseline and 6 months after injury
measure: Change in motor threshold between groups (Difference in %Maximum Stimulator Output to achieve motor threshold)
timeFrame: Baseline and 6 months after injury
Other outcomes:
Locations:
city: Elkins Park
country: United States
facility: Jefferson Moss-Magee Rehabilitation - Elkins Park
state: Pennsylvania
Study officials:
affiliation: Albert Einstein Healthcare Network
name: Dylan J Edwards, PhD
role: PRINCIPAL_INVESTIGATOR
References: