Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) as an Anti-inflammatory Strategy for the Treatment of Depression Following Spinal Cord Injury
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- Incidence of Treatment-Emergent Adverse Events During Intervention
研究概览
简要总结
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.
详细描述
Depression and chronic inflammation are highly prevalent following SCI Inflammation plays an increasingly appreciated role in the pathology of depression. One key mechanism is the ability to dysregulate a key metabolic pathway (the Kynurenine pathway) resulting in serotonin deficits and increased production of neurotoxic metabolites. Prior research from our lab has demonstrated the efficacy of diet and exercise to affect this pathway and improve clinical symptoms. However, we have shown that the burdensome nature of such interventions limits long-term adherence in SCI. Stimulating the vagus nerve has been shown to induce anti-inflammatory effects in populations with chronic inflammation (e.g. rheumatoid arthritis; Crohn's disease) and lower scores of depression.
However, the potential benefits of a chronic vagus nerve stimulation intervention has not been assessed in individuals with SCI. Transcutaneous auricular vagus nerve stimulation (taVNS) is a simple to administer and non-invasive neurostimulatory technique which can stimulate the vagus nerve via the skin of the ear. Given that SCI is associated with chronic inflammation, high rates of depression, and reductions in vagal tone, they may represent a population that would be particularly susceptible to the benefits of this low-burden, low-cost treatment strategy.
The overall objective of this study is to demonstrate that transcutaneous auricular vagus nerve stimulation (taVNS) therapy is a safe and feasible treatment which effectively activates the vagus nerve in individuals with SCI. The study will also provide preliminary efficacy data related to the impact on symptoms of depression and inflammatory biomarkers.
Participants will be randomized to receive either active taVNS therapy (treatment group), or sham taVNS therapy (placebo group). The intervention will be performed over a 30-day period and will follow the recommended daily stimulation of 4-hours per day with at least 1-hour carried out continuously (for a total of 30 sessions).
All participants will have an in-person baseline visit to determine optimal taVNS stimulation parameters and be trained on instructions for use. For the active stimulation group, stimulation will target the auricular branch of the vagus nerve by applying stimulation to the cymba conchae region of the left ear using the tVNS R device (taVNS Technologies, Erlangen, Germany). For the sham group, stimulation will target the earlobe, which will allow the participant to feel the stimulation, while avoiding stimulation of the auricular branch of the vagus nerve. 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 our previous protocol in spinal cord injured patients (approved by Health Canada: 364351 and shown to safely and effectively increase vagal tone). The stimulation parameters determined during this in-person baseline visit will be locked for the duration of the 30-day intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SCI of any level or severity
- •18 years of age or older
- •scores suggesting mild - moderately severe depression on the PHQ-9 (5 - 19)
- •stable dose of depression medications
排除标准
- •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.
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events During Intervention
时间窗: 30 days
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.
Change in Root Mean Square of Successive Differences (RMSSD)
时间窗: 30 days
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.
次要结局
- Change in High Frequency (HF) Power(30 days)
- Change in Plasma Cytokines(30 Days)
- Change in Plasma Kynurenines(30 days)
- Change in Symptoms of Depression(30 days)
- Program Adherence Rates(30 Days)