Transauricular Vagus Nerve Stimulation for Chronic Whiplash Associated Disorders

University of Calgary

Status: Not yet enrolling

Conditions: Whiplash Associated Disorder (WAD)

Treatments: Device: Transauricular Vagal Nerve Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT07055373

REB25-0529

Details and patient eligibility

About

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.

Full description

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.

The specific objectives of this study are as follows:

1. 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.
2. The secondary exploratory objectives are to evaluate neck pain intensity and associated disability, pain sensitivity, HRV, blood pressure, quality of life, post-traumatic stress, stress, anxiety, and depression - as measured by questionnaires and physical assessments - following active taVNS compared to sham taVNS in patients with WAD.

This will be a randomized, sham-controlled, participant and assessor blinded, pilot trial evaluating the safety and feasibility of taVNS for the treatment of WAD symptoms. Consenting and eligible participants will be asked to complete baseline questionnaires, physicial measurements (height, weight, and BMI), and clinical measurements. Questionnaires and physical measurements will be repeated immediately 1 month post taVNS and at 8-10 & 16 weeks. Participants will be be asked to refrain from taking prescribed medications, performing physical exercise, or consuming alcohol or coffee on day of testing. Blood pressure, heart rate variability, and pupillary light reflex measures will be performed. Participants will be instructed on use of a taVNS device including precautions and safety information.

Following study enrolment, participants will be randomized into one of two groups: active taVNS or sham taVNS. Randomization will occur via a sealed envelope where participant numbers have been sorted into active or sham taVNS by a random number generator. Participants in the sham group will be blinded using a previously established blinding method. They will undergo a 30 second ramp up period, during which, the current will be gradually increased and then the machine will reduce the waveform to 0 whilst remaining in the 'on' mode. Assessors will be blinded to the participants grouping.

Transauricular VNS will be administered using the Nurosym aVNT (auricular vagal neuromodulation therapy) Device (Parasym, London, UK). The Nurosym aVNT Device delivers non-invasive neuromodulation targeting the auricular branch of the vagus nerve via the tragus of the outer ear. All participants will receive four weeks of twice daily (morning and evening) 45-minute sessions of taVNS (frequency ≥ 25Hz; pulse width =250µs.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Symptom duration ≥3 months and <10 years; and
2. 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);
3. Average pain intensity (over one week) ≥ 4/10;
4. Neck Disability Index score > 28% (14/50).

Exclusion criteria

1. WAD IV injury (no neurological deficit, fracture, or dislocation);
2. Concussion symptoms;
3. Patients who have undergone cervical vagotomy;
4. Patients diagnosed with severe bradycardia;
5. Patients with a permanent implanted metallic or electronic device or jewellery at close proximity to the ear tragus;
6. 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);
7. 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
8. Using medications associated with ANS function such as Beta Blockers;
9. 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;
10. History of any mental health conditions prior to the MVC, such as bipolar disorder, schizophrenia, anxiety, PTSD or severe depression;
11. People who are unable to complete the questionnaires.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups

Active Transauricular Vagal Nerve Stimulation

Active Comparator group

Description:

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.

Treatment:

Device: Transauricular Vagal Nerve Stimulation

Sham Transauricular Vagal Nerve Stimulation

Sham Comparator group

Description:

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.

Treatment:

Device: Transauricular Vagal Nerve Stimulation