Vagus Nerve Stimulation + Rehabilitation for Spinal Cord Injury

Overseen by Radha Korupolu, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Neurotransmitter drugs

Disqualifiers: Non-traumatic SCI, Brain injury, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses a device that sends electrical signals to a nerve in the neck while patients do exercises. It targets adults with partial spinal cord injuries in the neck area who struggle with arm and hand movement. The electrical signals may help improve how the brain and nerves respond to exercise, aiding recovery.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those on medication that may interfere with the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Vagus Nerve Stimulation + Rehabilitation for Spinal Cord Injury?

Research shows that pairing vagus nerve stimulation (VNS) with rehabilitation can significantly improve motor recovery after spinal cord injury (SCI). Studies in animal models have demonstrated that VNS enhances recovery of forelimb function and strengthens neural connections, suggesting its potential as a beneficial treatment for SCI. ^{1 2 3 4 5}

Is Vagus Nerve Stimulation safe for humans?

Research on Vagus Nerve Stimulation (VNS) in a rat model of spinal cord injury suggests it is generally safe, as it did not cause prolonged low blood pressure or trigger severe autonomic reactions. These findings support further investigation into its safety for humans. ^{1 5 6 7 8}

How does vagus nerve stimulation treatment differ from other treatments for spinal cord injury?

Vagus nerve stimulation (VNS) is unique because it involves delivering electrical impulses to the vagus nerve, which can enhance the brain's ability to rewire itself and improve motor recovery when paired with rehabilitation. Unlike other treatments, VNS specifically targets neural plasticity, helping to restore connections in the nervous system and improve motor function after spinal cord injury. ^{1 2 3 9 10}

Research Team

Radha Korupolu, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

This trial is for individuals at least 12 months post-traumatic cervical spinal cord injury (C8 and above), with some upper limb movement, like pinching. They must meet surgical criteria for VNS implantation. Excluded are those with non-traumatic SCI, vocal cord issues, significant brain injuries, prior vagus nerve damage, certain medications affecting neurotransmitters, other complicating conditions or surgeries, medical or mental instability, or pregnancy.

Inclusion Criteria

I am eligible for a VNS implant surgery as per my medical team.

I have a spinal cord injury in my neck that is not complete.

It has been over a year since my spinal cord injury.

Exclusion Criteria

I have a significant brain injury.

I am not on medication that affects how VNS works on my brain chemicals.

Medical or mental instability

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 18 goal-directed upper extremity rehabilitation therapy sessions with paired or sham VNS over six weeks

6 weeks

18 visits (in-person)

Home Exercise Program

Participants engage in a daily, 30-minute home therapy program

90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

3 visits (in-person)

Treatment Details

Interventions

• Active VNS (Vagus Nerve Stimulation)
• Arm rehabilitation (Behavioural Intervention)
• Sham VNS (Vagus Nerve Stimulation)

Trial Overview The study tests the safety and effectiveness of pairing vagus nerve stimulation (VNS) with arm rehabilitation to improve upper extremity function in people with cervical spinal cord injury. Participants will receive either active VNS or a sham procedure alongside their rehabilitation exercises.

Participant Groups

Group I: Treatment group Experimental Treatment 2 Interventions

Participants in the treatment group will receive 18 goal-directed upper extremity rehabilitation therapy sessions with paired VNS over six weeks. Followed by 90 days home exercise program.

Group II: Control Group Placebo Group 2 Interventions

Participants in the control group will receive 18 goal-directed upper extremity rehabilitation therapy sessions with sham VNS over six weeks. Followed by 90 days home exercise program.

Active VNS is already approved in Canada for the following indications:

Approved in Canada as VNS Therapy for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Dr. LaTanya Love

The University of Texas Health Science Center, Houston

Interim President

MD from UT Medical Branch in Galveston

Dr. Jagat Narula

The University of Texas Health Science Center, Houston

Chief Academic Officer since 2023

MD, PhD

MicroTransponder Inc.

Industry Sponsor

Trials

8

Recruited

1,300+

Findings from Research

Intermittent vagus nerve stimulation (VNS) was found to be safe in a rat model of chronic spinal cord injury (SCI), showing only temporary effects on heart rate without causing prolonged hypotension or exacerbating autonomic dysreflexia.

The study suggests that VNS could enhance recovery and promote plasticity in neurological disorders, warranting further research into its therapeutic potential following SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Cardiovascular Responses to Vagus Nerve Stimulation after Experimental Spinal Cord Injury. Sachdeva, R., Krassioukov, AV., Bucksot, JE., et al.[2022]

Closed-loop vagus nerve stimulation (CLV) significantly enhances recovery of forelimb function in rats after chronic spinal cord injury (SCI), outperforming rehabilitation alone.

CLV works by strengthening synaptic connections in the brain that control movement, and its benefits continue even after stimulation ends, indicating lasting improvements in neural circuit connectivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-loop neuromodulation restores network connectivity and motor control after spinal cord injury. Ganzer, PD., Darrow, MJ., Meyers, EC., et al.[2019]

In a study involving rats with bilateral incomplete spinal cord injuries at C7/8, closed-loop vagus nerve stimulation (VNS) combined with rehabilitative training significantly improved forelimb strength recovery compared to training alone.

The positive effects of VNS on recovery were observed not only in trained tasks but also generalized to untrained forelimb tasks, suggesting that VNS can enhance rehabilitation outcomes even when alpha motor neurons are damaged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Rehabilitative Training Enhances Motor Recovery After Bilateral Spinal Cord Injury to Cervical Forelimb Motor Pools. Darrow, MJ., Torres, M., Sosa, MJ., et al.[2021]

In patients with spinal cord injuries (SCI) at cervical or thoracic levels, disturbances in autonomic nervous system (ANS) control were found to be more pronounced in those with cervical lesions, indicating a greater loss of sympathetic modulation during sleep and orthostatic challenges.

Despite these disturbances, vagally mediated baroreflexes remained largely intact across all patients, suggesting that some autonomic functions can still be preserved even after significant injury, although overall cardiovascular variability was negatively impacted, especially in cervical SCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Spinal Cord Injury Site on Cardiac Autonomic Regulation: Insight from Analysis of Cardiovascular Beat by Beat Variability during Sleep and Orthostatic Challenge. Guaraldi, P., Malacarne, M., Barletta, G., et al.[2022]

In a study of 31 patients with chronic spinal cord injuries, those with tetraplegia showed significant reductions in heart rate variability, indicating depressed autonomic nervous system activity compared to those with paraplegia.

Despite the reduced heart rate variability in tetraplegia patients, the overall balance between sympathetic and parasympathetic activity remained stable, suggesting that their autonomic nervous system maintained homeostasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased autonomic nervous system activity as assessed by heart rate variability in patients with chronic tetraplegia. Wang, YH., Huang, TS., Lin, JL., et al.[2022]

Electrical spinal cord stimulation (SCS) shows promise in improving autonomic functions related to exercise, particularly in individuals with spinal cord injuries, as evidenced by a review of 19 studies.

While improvements in blood pressure regulation were systematically studied, other benefits like temperature regulation and metabolism were mostly anecdotal, indicating a need for further research to optimize SCS parameters and locations for enhancing sympathetic functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal electrical stimulation to improve sympathetic autonomic functions needed for movement and exercise after spinal cord injury: a scoping clinical review. Flett, S., Garcia, J., Cowley, KC.[2022]

This study is a randomized controlled trial involving 120 adults with spinal cord injury (SCI) to evaluate the effectiveness of a neuro-cardiac self-regulation therapy (HRV-F) over 10 weeks, focusing on improving autonomic function and brain activity.

The primary outcomes will assess heart rate variability and cerebral blood circulation, while secondary outcomes will include various measures of psychological and physical health, aiming to determine if HRV-F can enhance overall well-being in individuals with SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A neuro-cardiac self-regulation therapy to improve autonomic and neural function after SCI: a randomized controlled trial protocol. Craig, A., Pozzato, I., Arora, M., et al.[2021]

Combining spinal cord stimulation with activity-based training shows improved outcomes in walking, muscle activation, and autonomic functions in individuals with spinal cord injury, based on a review of 15 studies involving 79 participants.

While the combination therapy appears to enhance recovery beyond traditional methods, the current evidence is limited, and more large-scale randomized trials are needed to establish standardized protocols and outcome measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When the whole is greater than the sum of its parts: a scoping review of activity-based therapy paired with spinal cord stimulation following spinal cord injury. Shackleton, C., Hodgkiss, D., Samejima, S., et al.[2022]

The VNS-REHAB trial aims to evaluate the safety and efficacy of vagus nerve stimulation (VNS) combined with upper limb rehabilitation in improving motor function in stroke patients, involving up to 120 participants with upper limb weakness due to stroke.

Preliminary studies suggest that VNS paired with rehabilitation leads to clinically meaningful improvements in motor function compared to rehabilitation alone, supporting the need for this larger pivotal trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. Kimberley, TJ., Prudente, CN., Engineer, ND., et al.[2023]

A systematic review of five randomized controlled trials involving 178 stroke patients showed that vagus nerve stimulation (VNS) combined with rehabilitation significantly improves upper extremity function, as measured by the Fugl-Meyer assessment.

The study found no significant adverse effects associated with VNS, suggesting it is a safe addition to rehabilitation therapies for enhancing recovery after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Combined Vagus Nerve Stimulation on Recovery of Upper Extremity Function in Patients with Stroke: A Systematic Review and Meta-Analysis. Liu, Y., Zhang, L., Zhang, X., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Acute Cardiovascular Responses to Vagus Nerve Stimulation after Experimental Spinal Cord Injury. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Closed-loop neuromodulation restores network connectivity and motor control after spinal cord injury. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Rehabilitative Training Enhances Motor Recovery After Bilateral Spinal Cord Injury to Cervical Forelimb Motor Pools. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Spinal Cord Injury Site on Cardiac Autonomic Regulation: Insight from Analysis of Cardiovascular Beat by Beat Variability during Sleep and Orthostatic Challenge. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Decreased autonomic nervous system activity as assessed by heart rate variability in patients with chronic tetraplegia. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Spinal electrical stimulation to improve sympathetic autonomic functions needed for movement and exercise after spinal cord injury: a scoping clinical review. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A neuro-cardiac self-regulation therapy to improve autonomic and neural function after SCI: a randomized controlled trial protocol. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

When the whole is greater than the sum of its parts: a scoping review of activity-based therapy paired with spinal cord stimulation following spinal cord injury. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Effect of Combined Vagus Nerve Stimulation on Recovery of Upper Extremity Function in Patients with Stroke: A Systematic Review and Meta-Analysis. [2022]