Clinical trial NCT05730049: Neuromodulation as an Anti-inflammatory Treatment in SCI
Official title: Assessing the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation as an Anti-inflammatory Treatment Following Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Inflammation
Keywords: Vagus Nerve Stimulation
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2023-02-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible participants who consent to study participation will be randomized to one of two groups: active taVNS, or sham taVNS. Each group will undergo 1 hour of the respective treatment.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Serum Biomarkers Immediately Following Intervention
timeFrame: Baseline - Immediately Following Intervention
measure: Change in Serum Biomarkers 24-hours Following Intervention
timeFrame: Baseline - 24-hour Post Intervention
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events During or Immediately Following Intervention
timeFrame: Immediately Following Intervention
measure: Incidence of Treatment-Emergent Adverse Events 24-hours Following Intervention
timeFrame: 24-hour Post intervention
measure: Time required to recruit 30 participants
timeFrame: Immediately following 6-month recruitment period
measure: Program Completion Rates
timeFrame: Immediately after intervention
measure: Participant Satisfaction with Intervention
timeFrame: 24-hour Post intervention
Other outcomes:
Locations:
city: London
country: Canada
facility: Parkwood Institute, St Joseph's Health Care London
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: David J. Allison, PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Allison DJ, Ditor DS. The common inflammatory etiology of depression and cognitive impairment: a therapeutic target. J Neuroinflammation. 2014 Sep 2;11:151. doi: 10.1186/s12974-014-0151-1.
citation: Tynan A, Brines M, Chavan SS. Control of inflammation using non-invasive neuromodulation: past, present and promise. Int Immunol. 2022 Jan 22;34(2):119-128. doi: 10.1093/intimm/dxab073.
citation: Redgrave JN, Moore L, Oyekunle T, Ebrahim M, Falidas K, Snowdon N, Ali A, Majid A. Transcutaneous Auricular Vagus Nerve Stimulation with Concurrent Upper Limb Repetitive Task Practice for Poststroke Motor Recovery: A Pilot Study. J Stroke Cerebrovasc Dis. 2018 Jul;27(7):1998-2005. doi: 10.1016/j.jstrokecerebrovasdis.2018.02.056. Epub 2018 Mar 23.
citation: Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6.