Vagus Nerve Stimulation + Rehabilitation for Spinal Cord Injury

Overseen By Alyssa Miller

Age: 18+

Sex: Any

Trial Phase: Academic

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 All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether vagus nerve stimulation (VNS) can be safely and effectively combined with rehabilitation for people with spinal cord injuries. The trial includes two groups: one receives VNS during therapy sessions, while the other receives a sham (inactive) version. It targets individuals who have experienced a traumatic spinal cord injury in the neck area for over a year and can still move their upper limbs slightly, such as pinching with their fingers. The goal is to determine if VNS can improve recovery when added to regular rehabilitation exercises. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance rehabilitation outcomes for spinal cord injuries.

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 prior data suggests that vagus nerve stimulation is safe for spinal cord injury rehabilitation?

Research shows that vagus nerve stimulation (VNS) is generally safe for people. Studies have found that combining VNS with rehabilitation is safe for those with spinal cord injuries. One study examined the safety and feasibility of combining VNS with rehabilitation therapy and found it to be both safe and feasible. Another study assessed the safety of VNS using a device called the ReStore system and found it well-tolerated.

While VNS is usually safe, some participants in these studies experienced mild side effects, such as hoarseness, coughing, or a slight tingling sensation. Overall, the evidence suggests that VNS is a safe option for those considering participation in a clinical trial for spinal cord injury rehabilitation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the potential of Vagus Nerve Stimulation (VNS) paired with rehabilitation for spinal cord injury recovery. Unlike traditional treatments that focus solely on physical therapy, this approach combines targeted rehabilitation exercises with electrical stimulation of the vagus nerve, aiming to enhance neuroplasticity and improve motor function. This unique method could offer a more effective recovery process, potentially accelerating progress and improving outcomes for patients with spinal cord injuries. By integrating VNS, the trial seeks to unlock new pathways for healing that current standard care options, which typically rely on physical therapy alone, do not address.

What evidence suggests that pairing vagus nerve stimulation with rehabilitation could be effective for spinal cord injury?

Research has shown that combining vagus nerve stimulation (VNS) with rehabilitation can improve movement. In this trial, participants in the treatment group will receive active VNS paired with rehabilitation therapy, which previous studies have shown leads to significant improvements in arm and hand movement for people with spinal cord injuries. Meanwhile, the control group will receive sham VNS with rehabilitation therapy. Studies on stroke patients have also found that VNS with rehab aids in movement recovery, suggesting that VNS might help people regain movement after nerve-related injuries. The treatment stimulates the vagus nerve, enhancing the brain's ability to heal and reorganize itself. This makes VNS a promising option for improving recovery after spinal cord injuries. ^{1 2 4 6 7}

Who Is on the Research Team?

Radha Korupolu, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Active VNS
• Arm rehabilitation
• Sham VNS

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as VNS Therapy for:

• Epilepsy
• Depression
• Obesity

Approved in European Union as VNS Therapy for:

• Epilepsy
• Depression

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+

MicroTransponder Inc.

Industry Sponsor

Trials

8

Recruited

1,300+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. nature.com nature.com/articles/s41586-025-09028-5

Closed-loop vagus nerve stimulation aids recovery from ... Decades of research have demonstrated that recovery from serious neurological injury will require synergistic therapeutic approaches.

2. news.utdallas.edu news.utdallas.edu/health-medicine/vns-human-trial-spinal-cord-injuries-2025/

VNS Clinical Trial Shows Improvements for Spinal Cord Injuries This approach, called closed-loop vagus nerve stimulation (CLV), produced meaningful improvements in arm and hand function in these individuals.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06351111

Vagus Nerve Stimulation (VNS) in Spinal Cord Injury (SCI) ... This study is an open label extension of the SCI EFS clinical trial (NCT04288245) that developed an innovative strategy to enhance recovery of motor and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11604078/

Safety and feasibility of paired vagus nerve stimulation with ... Pairing vagus nerve stimulation with traditional rehabilitation therapies results in improved motor recovery in people with stroke.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38872818/

Neurorehabilitation with vagus nerve stimulation: a systematic ... Our review suggests that VNS (non-invasive or invasive) paired with rehabilitation can improve motor outcomes after stroke in humans.

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf/p970003s207b.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) This study was designed to confirm the efficacy and safety of vagus nerve stimulation established in the controlled portion of the E-03 Study. Two weeks ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39610700/

Safety and feasibility of paired vagus nerve stimulation with ... Safety and feasibility of paired vagus nerve stimulation with rehabilitation for improving upper extremity function in people with cervical spinal cord injury: ...