Transauricular Vagus Nerve Stimulation for Chronic Whiplash Associated Disorders

NCT07055373 | Recruiting

• 1 other identifier: REB25-0529
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Whiplash Associated Disorder (WAD)

Keywords

Whiplash Associated Disorder (WAD); Vagus Nerve Stimulation; Parasympathetic Nervous System; Sympathetic Nervous System; Post-traumatic Stress; Central Sensitization; Heart Rate Variability; Pupillometry

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events (AEs); recruitment rate; attendance rate; retention rate.

  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.

  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.

Secondary Outcomes (10)

• 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.

Other Outcomes (1)

• taVNS Diary

  To be completed twice daily during 4 weeks of taVNS treatment.

Study Arms (2)

Active Transauricular Vagal Nerve Stimulation

ACTIVE COMPARATOR

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.

Device: Transauricular Vagal Nerve Stimulation

Sham Transauricular Vagal Nerve Stimulation

SHAM COMPARATOR

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.

Device: Transauricular Vagal Nerve Stimulation

Interventions

Transauricular Vagal Nerve Stimulation DEVICE

Transauricular VNS will be administered using the Parasym aVNT (auricular vagal neuromodulation therapy) Device (Nurosym, London, UK). The Parasym 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 (Fig). The safety and tolerability of taVNS has been demonstrated in seven studies with a total of 205 (116 active, 121 sham) cardiovascular patients. Stimulation protocols ranged from 43 min to 8 hrs daily, for 1 day to 6 months. There were no device-related serious adverse events. Three patients (1.5%) experienced minor adverse events, i.e., dermal paresthesias (light tingling at the ear). No differences in tolerability were observed between active and sham taVNS \[21\].

Also known as: taVNS

Active Transauricular Vagal Nerve Stimulation; Sham Transauricular Vagal Nerve Stimulation

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vivo Cura Health: collaborator
• University of Calgary: lead

Study Sites (1)

Vivo Cura Health

Calgary, Alberta, T2E 2P5, Canada

RECRUITING

Related Publications (38)

• Wasylynuk C, Smith A. The Relationship Between Clinical Measures of Nociplastic Pain and Pupillary Light Reflex Measures in Chronic WAD. An observational study. 2024 IFOMPT. Basel, Switzerland2024.

  BACKGROUND

• Tracy LM, Ioannou L, Baker KS, Gibson SJ, Georgiou-Karistianis N, Giummarra MJ. Meta-analytic evidence for decreased heart rate variability in chronic pain implicating parasympathetic nervous system dysregulation. Pain. 2016 Jan;157(1):7-29. doi: 10.1097/j.pain.0000000000000360.

  PMID: 26431423 BACKGROUND

• Forte G, Troisi G, Pazzaglia M, Pascalis V, Casagrande M. Heart Rate Variability and Pain: A Systematic Review. Brain Sci. 2022 Jan 24;12(2):153. doi: 10.3390/brainsci12020153.

  PMID: 35203917 BACKGROUND

• Koenig J, Falvay D, Clamor A, Wagner J, Jarczok MN, Ellis RJ, Weber C, Thayer JF. Pneumogastric (Vagus) Nerve Activity Indexed by Heart Rate Variability in Chronic Pain Patients Compared to Healthy Controls: A Systematic Review and Meta-Analysis. Pain Physician. 2016 Jan;19(1):E55-78.

  PMID: 26752494 BACKGROUND

• Gockel M, Lindholm H, Niemisto L, Hurri H. Perceived disability but not pain is connected with autonomic nervous function among patients with chronic low back pain. J Rehabil Med. 2008 May;40(5):355-8. doi: 10.2340/16501977-0172.

  PMID: 18461260 BACKGROUND

• Meints SM, Garcia RG, Schuman-Olivier Z, Datko M, Desbordes G, Cornelius M, Edwards RR, Napadow V. The Effects of Combined Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation and Mindfulness Meditation for Chronic Low Back Pain: A Pilot Study. Pain Med. 2022 Aug 31;23(9):1570-1581. doi: 10.1093/pm/pnac025.

  PMID: 35148407 BACKGROUND

• Sator-Katzenschlager SM, Scharbert G, Kozek-Langenecker SA, Szeles JC, Finster G, Schiesser AW, Heinze G, Kress HG. The short- and long-term benefit in chronic low back pain through adjuvant electrical versus manual auricular acupuncture. Anesth Analg. 2004 May;98(5):1359-64, table of contents. doi: 10.1213/01.ane.0000107941.16173.f7.

  PMID: 15105215 BACKGROUND

• Stavrakis S, Chakraborty P, Farhat K, Whyte S, Morris L, Abideen Asad ZU, Karfonta B, Anjum J, Matlock HG, Cai X, Yu X. Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. JACC Clin Electrophysiol. 2024 Feb;10(2):346-355. doi: 10.1016/j.jacep.2023.10.015. Epub 2023 Nov 22.

  PMID: 37999672 BACKGROUND

• Geng D, Liu X, Wang Y, Wang J. The effect of transcutaneous auricular vagus nerve stimulation on HRV in healthy young people. PLoS One. 2022 Feb 10;17(2):e0263833. doi: 10.1371/journal.pone.0263833. eCollection 2022.

  PMID: 35143576 BACKGROUND

• Uzlifatin Y, Arfianti L, Wardhani IL, Hidayati HB, Melaniani S. Effect of transcutaneous auricular vagus nerve stimulation in addition to exercises on disabilitiy in chronic low back pain patients: A randomized controlled study. Anaesth Pain Intensive Care 2023; 21(1):73-81.

  BACKGROUND

• Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, Dore CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb 5;158(3):200-7. doi: 10.7326/0003-4819-158-3-201302050-00583.

  PMID: 23295957 BACKGROUND

• Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, Zeiss E. Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: redefining "whiplash" and its management. Spine (Phila Pa 1976). 1995 Apr 15;20(8 Suppl):1S-73S. No abstract available.

  PMID: 7604354 BACKGROUND

• Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics 2005;4(4):287-291.

  BACKGROUND

• Luche G, Dundovic S, Stavrakis S. REPORT OF SAFETY AND TOLERABILITY OF LOW-LEVEL TRAGUS VAGAL NEUROMODULATION IN CARDIOVASCULAR PATIENTS. JACC 2024;83:13:178.

  BACKGROUND

• Krebs EE, Lorenz KA, Bair MJ, Damush TM, Wu J, Sutherland JM, Asch SM, Kroenke K. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med. 2009 Jun;24(6):733-8. doi: 10.1007/s11606-009-0981-1. Epub 2009 May 6.

  PMID: 19418100 BACKGROUND

• Boonstra AM, Stewart RE, Koke AJ, Oosterwijk RF, Swaan JL, Schreurs KM, Schiphorst Preuper HR. Cut-Off Points for Mild, Moderate, and Severe Pain on the Numeric Rating Scale for Pain in Patients with Chronic Musculoskeletal Pain: Variability and Influence of Sex and Catastrophizing. Front Psychol. 2016 Sep 30;7:1466. doi: 10.3389/fpsyg.2016.01466. eCollection 2016.

  PMID: 27746750 BACKGROUND

• Master CL, Podolak OE, Ciuffreda KJ, Metzger KB, Joshi NR, McDonald CC, Margulies SS, Grady MF, Arbogast KB. Utility of Pupillary Light Reflex Metrics as a Physiologic Biomarker for Adolescent Sport-Related Concussion. JAMA Ophthalmol. 2020 Nov 1;138(11):1135-1141. doi: 10.1001/jamaophthalmol.2020.3466.

  PMID: 32970102 BACKGROUND

• Podolak OE, Arbogast KB, Nabin JB, Ciuffreda K, Grady M, Master CL. The use Of Pupillary Light Reflex in Concussed Athletes. Orthopaedic Journal of Sports Medicine 2020;8(4_suppl3):2325967120S00277.

  BACKGROUND

• Wan AK, Rainville P, O'Leary S, Elphinston RA, Sterling M, Lariviere C, Sullivan MJL. Validation of an index of Sensitivity to Movement-Evoked Pain in patients with whiplash injuries. Pain Rep. 2018 Jun 20;3(4):e661. doi: 10.1097/PR9.0000000000000661. eCollection 2018 Jul-Aug.

  PMID: 30123856 BACKGROUND

• Smith A, Pedler A. Conditioned pain modulation is affected by occlusion cuff conditioning stimulus intensity, but not duration. Eur J Pain. 2018 Jan;22(1):94-102. doi: 10.1002/ejp.1093. Epub 2017 Aug 14.

  PMID: 28805288 BACKGROUND

• Yarnitsky D, Bouhassira D, Drewes AM, Fillingim RB, Granot M, Hansson P, Landau R, Marchand S, Matre D, Nilsen KB, Stubhaug A, Treede RD, Wilder-Smith OH. Recommendations on practice of conditioned pain modulation (CPM) testing. Eur J Pain. 2015 Jul;19(6):805-6. doi: 10.1002/ejp.605. Epub 2014 Oct 20.

  PMID: 25330039 BACKGROUND

• Jobin K, Smith A, Campbell C, Schabrun SM, Galarneau JM, Schneider KJ, Debert CT. The safety and feasibility of transcranial direct current stimulation and exercise therapy for the treatment of cervicogenic headaches: A randomized pilot trial. Headache. 2025 May;65(5):845-862. doi: 10.1111/head.14887. Epub 2025 Jan 17.

  PMID: 39825590 BACKGROUND

• Robinson-Papp J, George MC, Wongmek A, Nmashie A, Merlin JS, Ali Y, Epstein L, Green M, Serban S, Sheth P, Simpson DM. The Quantitative Analgesic Questionnaire: A Tool to Capture Patient-Reported Chronic Pain Medication Use. J Pain Symptom Manage. 2015 Sep;50(3):381-6. doi: 10.1016/j.jpainsymman.2015.03.013. Epub 2015 Apr 23.

  PMID: 25912277 BACKGROUND

• Stark RG, Reitmeir P, Leidl R, Konig HH. Validity, reliability, and responsiveness of the EQ-5D in inflammatory bowel disease in Germany. Inflamm Bowel Dis. 2010 Jan;16(1):42-51. doi: 10.1002/ibd.20989.

  PMID: 19475674 BACKGROUND

• Alhassani G, Treleaven J, Schabrun SSM. Combined transcranial and trans-spinal direct current stimulation in chronic headache: A feasibility and safety trial for a novel intervention. Hong Kong Physiother J. 2017 Feb 23;37:1-9. doi: 10.1016/j.hkpj.2016.11.001. eCollection 2017 Dec.

  PMID: 30931040 BACKGROUND

• Bovin MJ, Marx BP, Weathers FW, Gallagher MW, Rodriguez P, Schnurr PP, Keane TM. Psychometric properties of the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5) in veterans. Psychol Assess. 2016 Nov;28(11):1379-1391. doi: 10.1037/pas0000254. Epub 2015 Dec 14.

  PMID: 26653052 BACKGROUND

• Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress. 2015 Dec;28(6):489-98. doi: 10.1002/jts.22059. Epub 2015 Nov 25.

  PMID: 26606250 BACKGROUND

• Lovibond PF, Lovibond SH. The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. Behav Res Ther. 1995 Mar;33(3):335-43. doi: 10.1016/0005-7967(94)00075-u.

  PMID: 7726811 BACKGROUND

• Vernon H, Mior S. The Neck Disability Index: a study of reliability and validity. J Manipulative Physiol Ther. 1991 Sep;14(7):409-15.

  PMID: 1834753 BACKGROUND

• Hung M, Baumhauer JF, Licari FW, Voss MW, Bounsanga J, Saltzman CL. PROMIS and FAAM Minimal Clinically Important Differences in Foot and Ankle Orthopedics. Foot Ankle Int. 2019 Jan;40(1):65-73. doi: 10.1177/1071100718800304. Epub 2018 Oct 4.

  PMID: 30282469 BACKGROUND

• Young IA, Dunning J, Butts R, Cleland JA, Fernandez-de-Las-Penas C. Psychometric properties of the Numeric Pain Rating Scale and Neck Disability Index in patients with cervicogenic headache. Cephalalgia. 2019 Jan;39(1):44-51. doi: 10.1177/0333102418772584. Epub 2018 Apr 19.

  PMID: 29673262 BACKGROUND

• Hertzog MA. Considerations in determining sample size for pilot studies. Res Nurs Health. 2008 Apr;31(2):180-91. doi: 10.1002/nur.20247.

  PMID: 18183564 BACKGROUND

• Sim J, Lewis M. The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency. J Clin Epidemiol. 2012 Mar;65(3):301-8. doi: 10.1016/j.jclinepi.2011.07.011. Epub 2011 Dec 9.

  PMID: 22169081 BACKGROUND

• Tran N, Asad Z, Elkholey K, Scherlag BJ, Po SS, Stavrakis S. Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans. J Cardiovasc Transl Res. 2019 Jun;12(3):221-230. doi: 10.1007/s12265-018-9853-6. Epub 2018 Dec 17.

  PMID: 30560316 BACKGROUND

• White L, Smith AD, Farrell SF. Associations Between Resting Heart Rate, Resting Blood Pressure, Psychological Variables and Pain Processing in Chronic Whiplash-Associated Disorder: A Cross-Sectional Study. Pain Med. 2022 Oct 29;23(11):1882-1890. doi: 10.1093/pm/pnac075.

  PMID: 35587744 BACKGROUND

• Gaab J, Baumann S, Budnoik A, Gmunder H, Hottinger N, Ehlert U. Reduced reactivity and enhanced negative feedback sensitivity of the hypothalamus-pituitary-adrenal axis in chronic whiplash-associated disorder. Pain. 2005 Dec 15;119(1-3):219-224. doi: 10.1016/j.pain.2005.10.001. Epub 2005 Nov 17.

  PMID: 16298068 BACKGROUND

• Sterling M, Jull G, Kenardy J. Physical and psychological factors maintain long-term predictive capacity post-whiplash injury. Pain. 2006 May;122(1-2):102-8. doi: 10.1016/j.pain.2006.01.014. Epub 2006 Mar 9.

  PMID: 16527397 BACKGROUND

• Sterling M, Jull G, Vicenzino B, Kenardy J. Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery. Pain. 2003 Aug;104(3):509-517. doi: 10.1016/S0304-3959(03)00078-2.

  PMID: 12927623 BACKGROUND

Study Officials

• Ashley Smith

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Laxshimalla

CONTACT

403-265-3838; jennifer.laxshimalla@vivocura.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 9, 2025
• First Posted: July 8, 2025
• Study Start: January 21, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)