The Safety and Feasibility of Transauricular Vagus Nerve Stimulation Therapy in Chronic Whiplash-Associated Disorders: A Randomized Pilot Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Number of participants with treatment-related adverse events (AEs); recruitment rate; attendance rate; retention rate.
研究概览
简要总结
Approximately 50% of people with chronic whiplash-associated disorders (WAD) continue to report the presence of symptoms 12 months post-injury. These symptoms include high levels of pain and disability as well as psychological symptoms such as post-traumatic stress. The nervous system may also be affected, specifically the autonomic nervous system which is responsible for regulating heart rate and blood pressure.
An important part of the autonomic system is the vagus nerve, which helps regulate pain and stress responses. Treatment of this nerve via transauricular vagal nerve stimulation (taVNS) has been shown to improve health outcomes in many pain conditions such as chronic low back pain and postural tachycardia syndrome. TaVNS works by sending mild electrical pulses through the ear.
This project aims to explore whether or not taVNS can help people with chronic whiplash-associated disorders (WAD) feel better. The first goal is to evaluate the safety and feasibility of taVNS. The investigators are interested in learning how many people with chronic WAD participate in the study and how many complete the full treatment, as well as ensuring that the treatment does not cause any serious side effects. An additional goal is to evaluate the effects of taVNS on neck pain intensity and associated disability, pain sensitivity, heart rate variability, blood pressure, quality of life, post-traumatic stress, stress, anxiety, and depression as measured by questionnaires and physical assessments, as compared to those assigned to the sham treatment.
详细描述
Approximately 50% of people with chronic whiplash-associated disorders (WAD) continue to report the presence of symptoms 12 months post-injury. Many of these patients present with high levels of pain and disability and a heterogeneous presentation of both physical and psychological manifestations, inclusive of central nervous system hyperexcitability. Autonomic dysfunction has also been demonstrated in WAD.
Autonomic dysregulation via impaired peripheral vasoconstrictor responses has been demonstrated in both acute and chronic WAD, although the association with clinical features and health outcomes is unclear. Dysregulation of the hypothalamic-pituitary-adrenal axis (one of the key pathways to respond to stress) via reduced reactivity and enhanced negative feedback suppression has also been demonstrated in chronic WAD. In association with high levels of psychological distress and post-traumatic stress symptoms, stress system dysfunction in the form of autonomic nervous system (ANS) dysregulation is possible.
Previous resaerch by the investigators has demonstrated changes in autonomic function through heart rate and blood pressure measures in chronic WAD. More recently, the role of the ANS in chronic WAD has been examined using pupillometry. The results showed the presence of increased sympathetic nervous system activity, and reduced parasympathetic activity. These findings are consistent with those observed in other chronic pain conditions. This imbalance reportedly decreases the ANS adaptive response to both physical or emotional pain. These findings support the hypothesis that autonomic dysfunction potentially contributes to pain persistence.
An important link between the autonomic system and pain regulation mechanisms is the vagus nerve. Pain control occurs through vagally mediated afferent and efferent stimuli. The vagus nerve is also known to carry around 75% of parasympathetic fibers. Treatments affecting vagally mediated pain control includes non-invasive vagus nerve stimulation (VNS).
Transauricular VNS (taVNS) has been shown to improve health outcomes in many dysautonomic conditions and pain, such as chronic low back pain and postural tachycardia syndrome. Improvements in both biomarkers of autonomic dysfunction, such as heart rate variability (HRV); in association with reductions of pain and disability and improvements in pain sensitivity have been demonstrated, illustrating the potential of tVNS to modulate pain.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptom duration ≥3 months and <10 years; and
- •Classifiable as WAD grade I (neck pain without physical impairments) or II (neck pain & impairment such as movement loss and/or tenderness) or III (neck pain & neurological deficit evident on physical exam);
- •Average pain intensity (over one week) ≥ 4/10;
- •Neck Disability Index score > 28% (14/50).
排除标准
- •WAD IV injury (no neurological deficit, fracture, or dislocation);
- •Concussion symptoms;
- •Patients who have undergone cervical vagotomy;
- •Patients diagnosed with severe bradycardia;
- •Patients with a permanent implanted metallic or electronic device or jewellery at close proximity to the ear tragus;
- •Patients with any active implanted device (including electronic and/or medical devices) e.g. cochlear implant, cerebral shunts, invasive vagus nerve stimulators, or non-active but potentially interacting with the nervous system (e.g., metal implants);
- •Open wounds or rashes, swollen, red, infected, or inflamed areas or skin eruptions (e.g., phlebitis, thrombophlebitis, varicose veins); or cancerous lesions in the area of stimulation
- •Using medications associated with ANS function such as Beta Blockers;
- •Adverse general health factors such as presence of a neurological disorder (e.g., multiple sclerosis), inflammatory condition (e.g., rheumatoid arthritis), cardiovascular disorder (known severe coronary disease or recent myocardial infarction (within 5 years)); metabolic disorder (e.g., diabetes), visual deficit or disease process (e.g. cataracts, double or blurred vision), known or suspected serious spinal pathology (e.g. metastatic disease of the spine), pregnancy, or previous spinal surgery or recurrent treatment for spinal disorders;
- •History of any mental health conditions prior to the MVC, such as bipolar disorder, schizophrenia, anxiety, PTSD or severe depression;
- •People who are unable to complete the questionnaires.
研究组 & 干预措施
Active Transauricular Vagal Nerve Stimulation
Upon enrolment, participants randomized into the active treatment arm will be asked to complete a series of questionnaires seeking information on physical measurements (height, weight, & BMI), accident history, current symptoms, treatments received to date, and quality of life. Physical assessments will be performed to assess autonomic function and pain sensitivity including pupillary light reflex, heart rate variability, temporal summation, pressure pain thresholds, and conditioned pain modulation. Transauricular vagal nerve stimulation (taVNS) will be delivered a via a device that sends mild electrical pulses through the tragus of the outer ear. Participants will receive instructions device use in order to complete four weeks of twice daily (morning and evening) 45 minute sessions of taVNS. Follow ups will be completed immediately post intervention and at 4-6 weeks and 12 weeks 1 month post active taVNS. Participants will be asked to track device usage and report any adverse events.
干预措施: Transauricular Vagal Nerve Stimulation (Device)
Sham Transauricular Vagal Nerve Stimulation
Participants assigned to the sham treatment arm will be asked to complete all the same questionnaires and physical assessments as those assigned to the active treatment arm. They will also be provided with a taVNS device and instructions on use. The device will be programed by the research team to reduce the output to '0' and thus those assigned to the sham group will not actually be receiving any active treatment. Participants will not be able to distinguish if any treatment is being received.
干预措施: Transauricular Vagal Nerve Stimulation (Device)
结局指标
主要结局
Number of participants with treatment-related adverse events (AEs); recruitment rate; attendance rate; retention rate.
时间窗: The study duration is 4 months, including 1 month of self-administered taVNS. Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.
The primary objective is to evaluate the safety and feasibility of a randomized pilot study of taVNS as a treatment for patients with WAD in terms of recruitment (greater than 30%), attendance (70% total treatment time in a 4 week period), retention (greater than 70% complete protocol), safety (no severe adverse events and less than a 30% increase in adverse effects for the active group), and acceptability of the protocol.
次要结局
- Neck pain intensity as measured by the Numerical Pain Rating Scale, 0-10.(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- Neck-related disability as measured by the Neck Disability Index, 0-50.(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- Pain sensitivity as measured by Pressure Pain Thresholds in Newtons.(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- Temporal Summation as measured by NPRS, 0-10.(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- Sensitivity to pressure as measured by Conditioned Pain Modulation (% change from baseline).(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- Heart rate variability (RMSSD in ms).(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- Blood pressure recorded in mmHg.(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- Quality of life as measured by SF-12.(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- PTSD symptoms as measured by the PCL-5.(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
- Depression, anxiety, and stress via DASS-21.(Outcome measures will be assessed at baseline, immediately post-treatment (end of week 4) and during follow-ups at Week 8-10 and Week 16.)
研究者
Ashley Smith
Principal Investigator
University of Calgary