Neuromodulation as an Anti-inflammatory Treatment in SCI

NCT05730049 | Recruiting

• 1 other identifier: 12901
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries; Inflammation

Keywords

Vagus Nerve Stimulation

Outcome Measures

Primary Outcomes (2)

• Change in Serum Biomarkers Immediately Following Intervention

  Change in serum concentrations of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and interferon-gamma (IFN-y) immediately following intervention. Change in serum concentrations of acetylcholine immediately following intervention will be assessed as an indicator of the activity of the cholinergic anti-inflammatory pathway, and the change in cortisol immediately following intervention will be assessed as an indicator of the activity of the neuro-endo-immune pathway.

  Baseline - Immediately Following Intervention

• Change in Serum Biomarkers 24-hours Following Intervention

  Change in serum concentrations of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and interferon-gamma (IFN-y) 24-hours following intervention. Change in serum concentrations of acetylcholine 24-hours following intervention will be assessed as an indicator of the activity of the cholinergic anti-inflammatory pathway, and the change in cortisol 24-hours following intervention will be assessed as an indicator of the activity of the neuro-endo-immune pathway.

  Baseline - 24-hour Post Intervention

Secondary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events During or Immediately Following Intervention

  Immediately Following Intervention

• Incidence of Treatment-Emergent Adverse Events 24-hours Following Intervention

  24-hour Post intervention

• Time required to recruit 30 participants

  Immediately following 6-month recruitment period

• Program Completion Rates

  Immediately after intervention

• Participant Satisfaction with Intervention

  24-hour Post intervention

Study Arms (2)

Active taVNS

EXPERIMENTAL

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.

Device: Transcutaneous auricular vagus nerve stimulation

Sham taVNS

SHAM COMPARATOR

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.

Device: Transcutaneous auricular vagus nerve stimulation

Interventions

Transcutaneous auricular vagus nerve stimulation DEVICE

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(3). Pulse width will be set at 100μs and frequency will be set at 25Hz as performed in a previous protocol in stroke patients(3). 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(4).

Also known as: NEMOS® taVNS device

Active taVNS; Sham taVNS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

Parkwood Institute, St Joseph's Health Care London

London, Ontario, N6C 0A7, Canada

RECRUITING

Related Publications (4)

• 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.

  PMID: 25178630 BACKGROUND

• 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.

  PMID: 34558623 BACKGROUND

• 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.

  PMID: 29580658 BACKGROUND

• 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.

  PMID: 25573069 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; Inflammation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David J. Allison, PhD.

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David J Allison, PhD.

CONTACT

519 646 6100; David.Allison@sjhc.london.on.ca

Alexandria Roa Agudelo

CONTACT

519 646 6100; Alexandria.RoaAgudelo@sjhc.london.on.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 13, 2023
• First Posted: February 15, 2023
• Study Start: January 1, 2024
• Primary Completion: August 30, 2024
• Study Completion: August 31, 2024
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)