Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for Inflammation and Depression Following SCI
NCT Number: NCT06493071
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Spinal Cord Injury|Depression
Interventions: DEVICE: Active Transcutaneous Auricular Vagus Nerve Stimulation|DEVICE: Sham Transcutaneous Auricular Vagus Nerve Stimulation
Sponsor: Lawson Health Research Institute
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 44
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (PARTICIPANT)|Primary Purpose: TREATMENT
Start Date: 2024-10-01
Completion Date: 2026-08-30

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.

Primary Outcome Measures: 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 Outcome Measures: Change in High Frequency (HF) Power, Changes in autonomic function related to vagal tone will also be assessed via changes in high frequency (HF) power to confirm changes seen in root mean square of successive differences (RMSSD). HRV will be assessed via electrocardiogram (ECG). 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 HF power. HF Power will be assessed at baseline and post-intervention to assess whether the intervention successfully targets the vagus nerve and increases vagal tone., 30 days|Change in Symptoms of Depression, Depression will be assessed via the Patient Health Questionnaire (PHQ-9) at baseline, and 30-days (post-intervention). The PHQ-9 has been shown to be a valid assessment for major depressive disorder in individuals with SCI. The PHQ-9 is a 9-item questionnaire with items pertaining to feelings over the previous 2-weeks. Each item is scored on a scale from 0 ("not at all") to 3 ("nearly every day") with total scores allowing for assessment of depression severity. A score ranging from 0-4 suggests "none-minimal" depression severity, 5-9 suggests mild depression severity, 10-14 suggests moderate depression severity, 15-19 suggests moderately severe depression severity, and 20-27 suggests severe depression severity. A PHQ-9 score ≥ 10 has a sensitivity of 88% and a specificity of 88% for major depression., 30 days|Change in Plasma Cytokines, Blood samples (20 ml) will be collected by a certified phlebotomist at baseline and 30-days (post intervention) for the quantification of plasma cytokines (pg/ml). Plasma concentrations of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and interferon-gamma (IFN-y) will be quantified using 32x4 simple plex multianalyte cartridge for the Ella automated immunoassay system (ProteinSimple, San Jose, California). Each of the cytokines TNF-α, IL-1β, IL-6, and IFN-y have been shown to dysregulate the KYN pathway, while CRP is a ubiquitous measure of inflammation., 30 Days|Change in Plasma Kynurenines, Blood samples (20 ml) will be collected by a certified phlebotomist at baseline and 30-days (post intervention) for the quantification of plasma kynurenines (ng/ml). Plasma concentrations of the kynurenines tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) will be quantified in triplicate via enzyme-linked immunosorbent assay (ImmuSmol, Pessac, France)., 30 days|Program Adherence Rates, Adherence will be assessed each week by the number of days whereby participants completed the full 4-hour session., 30 Days