Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for Inflammation and Depression Following SCI

NCT06493071 | Recruiting

• 1 other identifier: 13842
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Spinal cord injury (SCI) has been shown to be associated with impairment to the autonomic nervous system in the form of reduced activity of a key nerve known as the vagus nerve. As the vagus nerve has an important role in regulating inflammation and is associated with depression, it may represent a key mechanism which contributes to chronic inflammation and depression following SCI. A technique known as transcutaneous auricular vagus nerve stimulation (taVNS) can stimulate the vagus nerve non-invasively through an electrode applied on the skin of the ear. This technique has been shown to effectively reduce inflammation and improve symptoms of depression in other populations without any serious adverse events. However, it has not been assessed in individuals with SCI. The primary objective of this study is to assess the efficacy of taVNS therapy for the treatment of inflammation and depression. Autonomic function as assessed by measures of heart rate variability (HRV) will also be assessed to quantify changes in vagal tone. The study will be conducted over a 2-year period, with 44 individuals with SCI and depression participating. Participants will be randomly assigned to receive either active taVNS or a placebo (sham) treatment over a 30-day period. The researchers will assess changes in depression symptoms, autonomic function (heart rate variability), and biomarkers related to inflammation at baseline and 30-days. Safety and adherence will also be evaluated to confirm the feasibility for long-term use. This study aims to explore a novel and non-invasive treatment strategy for depression in individuals with spinal cord injury. If taVNS is found to be safe, effective, and feasible for SCI patients, it could offer a simple, cost-effective way to address chronic inflammation and depression in this population.

Conditions

Spinal Cord Injury; Depression

Keywords

Vagus Nerve Stimulation; Inflammation; Kynurenine; Spinal Cord Injury; Depression

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events During Intervention

  All adverse events which occur during the intervention will be recorded during the twice weekly phone calls and/or study visits and compared between the active taVNS and sham taVNS conditions. A description of the adverse event, number of events, and total number of participants affected will be recorded.

  30 days

• Change in Root Mean Square of Successive Differences (RMSSD)

  HRV will be assessed via electrocardiogram (ECG) to assess changes in autonomic function related to vagal tone. Continuous heart rate will be recorded at rest for a period of 5-minutes to obtain a baseline measure. This process will be repeated following the 30-day intervention period at the post testing session. ECG data will be used for analysis of root mean square of successive differences (RMSSD). RMSSD will be assessed at baseline and post-intervention to assess whether the intervention successfully targets the vagus nerve and increases vagal tone.

  30 days

Secondary Outcomes (5)

• Change in High Frequency (HF) Power

  30 days

• Change in Symptoms of Depression

  30 days

• Change in Plasma Cytokines

  30 Days

• Change in Plasma Kynurenines

  30 days

• Program Adherence Rates

  30 Days

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).

Device: Active Transcutaneous Auricular Vagus Nerve Stimulation

Sham taVNS

SHAM COMPARATOR

Stimulation will target the ear lobe using the NEMOS® taVNS device (taVNS Technologies, Erlangen, Germany). Stimulation will be applied to the ear lobe in order to ensure participant feel the stimulation while avoiding activation of the vagus nerve.

Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation

Interventions

Active 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 tVNS R 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. Parameters will be set for the duration of the intervention consisting of 4 hours of daily stimulation for a period of 30 days.

Also known as: tVNS R

Active taVNS

Sham Transcutaneous Auricular Vagus Nerve Stimulation DEVICE

Stimulation will target the ear lobe 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. Participants will perform 4 hours of stimulation per day for a period of 30 days. Stimulation will be applied to the ear lobe in order to ensure participant feel the stimulation while avoiding activation of the vagus nerve.

Also known as: tVNS R

Sham taVNS

Eligibility Criteria

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

You may qualify if:

• SCI of any level or severity
• years of age or older
• scores suggesting mild - moderately severe depression on the PHQ-9 (5 - 19)
• stable dose of depression medications

You may not qualify if:

• Prone to autonomic dysreflexia
• Severe depression as assessed by PHQ-9 (≥20)
• Suicidal ideation
• presence of cardiovascular disease
• pacemaker or other implanted electrical device (e.g. cochlear implant, implanted vagus nerve stimulator, cardiac pacemaker)
• people with cerebral shunts
• people with epilepsy
• people who pregnant or attempting to become pregnant.

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

MeSH Terms

Conditions

Spinal Cord Injuries; Depression; Inflammation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Behavioral Symptoms; Behavior; 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

Joy Jiang

CONTACT

519 646 6100; fjiang63@uwo.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 30 days of the respective treatment.

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: July 9, 2024
• Study Start: January 27, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: February 7, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)