Neuromodulation as an Anti-inflammatory Treatment in SCI

Lawson Health Research Institute

Status: Enrolling

Conditions: Inflammation; Spinal Cord Injuries

Treatments: Device: Transcutaneous auricular vagus nerve stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT05730049

12901

Details and patient eligibility

About

The goal of this single-blinded randomized, controlled trial is to assess the impact of 1-hour of active transcutaneous auricular vagus nerve stimulation (taVNS) vs sham taVNS on serum biomarkers of the inflammatory reflex and inflammation in individuals with spinal cord injury.

The main question it aims to answer is: whether taVNS is a safe and effective anti-inflammatory intervention for individuals with SCI. Participants will perform a single 1-hour bout of the respective taVNS treatment with blood draws prior to treatment, immediately following treatment, and 24 hours following treatment. Changes in biomarkers between the active and sham taVNS conditions will be compared.

Full description

Chronic inflammation is very common among individuals living with spinal cord injury (SCI) and contributes to a number of health complications(1). Drug treatments are available to help reduce inflammation, however, many patients are unresponsive, become resistant or experience adverse effects such as increased risk of infection(2). There is a need for other treatments which reduce inflammation while avoiding harmful side effects.

It is now understood that the nervous systems plays an important role in regulating the immune system and controlling inflammation. The vagus nerve has been shown to be a particularly important part of the nervous system in terms of limiting inflammation. However, SCI causes disruption to the nervous system, including reduced activity of the vagus nerve. This may contribute to excessive inflammation. New technologies have been developed that allow the vagus nerve to be activated by electrically stimulating a part of the ear. This technique called vagus nerve stimulation (VNS) has been shown to help reduce inflammation in numerous populations. However, it has not been assessed in individuals with SCI. This study will assess if stimulating the vagus nerve can be a safe and effective way to reduce inflammation in individuals with SCI.

To assess this, 30 individuals with SCI who agree to participate will be randomly assigned to receive either active VNS treatment or sham treatment (whereby the device will placed in such a way that it does not stimulate the vagus nerve). Participants will not be aware of which group they are in. The study will take place over a 2-day period. On day one, participants will arrive in the morning for a fasted blood draw to assess baseline inflammation. Following the blood draw, participants will receive 1-hour of either the active or sham VNS therapy. Immediately following VNS therapy a second blood draw will be performed. On day 2 participants will be asked to return at the same time of day to complete a final fasted blood draw. This will allow for the assessment of how well the therapy activated 2 key anti-inflammatory pathways controlled by the vagus nerve and resulting changes in inflammation (immediate and 24-hour post).

It is expected that VNS therapy will be well-tolerated, safe and effective at reducing inflammation in individuals with SCI. If this is shown, VNS may prove to be a simple and cost-effective means of reducing chronic inflammation in individuals with SCI and may help to replace and/or reduce the need for other pharmaceutical drugs which are associated with adverse health outcomes.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Any level of severity of spinal cord injury
• 18 years of age or older

Exclusion criteria

• pregnant or attempting to become pregnant
• people with active implants (e.g. cochlear implant, implanted vagus nerve stimulator, cardiac pacemaker)
• people with cerebral shunts

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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30 participants in 2 patient groups

Active taVNS

Experimental group

Description:

Stimulation will target the auricular branch of the vagus nerve by applying stimulation to the cymba conchae region of the ear using the NEMOS® taVNS device (taVNS Technologies, Erlangen, Germany). To achieve adequate stimulation while avoiding unpleasant or painful sensations, the stimulation intensity will be gradually increased in increments of 0.1mA until the subjective pain threshold is reached, and then reduced to a stimulus intensity just below the individuals pain threshold (expected range based on prior studies 1 - 3.2mA. Pulse width will be set at 100μs and frequency will be set at 25Hz as performed in a previous protocol in stroke patients. Stimulation will be applied for a duration of 1 hour.

Treatment:

Device: Transcutaneous auricular vagus nerve stimulation

Sham taVNS

Sham Comparator group

Description:

The control group will receive the same stimulation parameters but will have the earpiece placed in the sham position such that stimulation is applied to the earlobe and does not activate the vagus nerve.

Treatment:

Device: Transcutaneous auricular vagus nerve stimulation