Personalized Auricular Vagus Nerve Stimulation in Intractable Chronic Low Back Pain

Study Overview
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Brief Summary
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One in five people in the general adult population suffer from chronic pain, a figure that is higher than heart disease, cancer, and diabetes combined. A majority of these patients is suffering from chronic back pain. Conventional treatment options offer only a partial response, with many people continuing to suffer severe chronic pain, despite receiving several treatments. Non-pharmacological treatments by neuromodulation represent a promising treatment modality for these patients. For instance, spinal cord stimulation blocks pain signals travelling to the brain, but requires implantation near the spine with significant clinical risks. Vagus nerve stimulation (VNS) is another neuromodulation modality proposed to alleviate chronic pain. Conventional VNS devices are implanted under the skin on the chest and the electrodes are wired to the left vagus nerve in the neck. However, aside from implantation risks, VNS is often associated with side effects such as swallowing difficulties, due to unwanted stimulation of motoric vagus nerve branches in the neck. Percutaneous auricular VNS (pVNS) is an emerging technology for stimulation of the auricular branch of the vagus nerve in the pinna of the ear. Specific electrical impulses are applied via three miniature needle electrodes located in the auricle near sensory vagus nerve fibers. Scientific data show that pVNS modulates brain circuits involved in autonomic control and pain processing. pVNS has shown positive effects in chronic low-back pain patients, in a sustainable way with a low side-effect profile. However, the optimal settings of stimulation with regards to personalization remain to be elucidated. The present prospective, open, randomized, controlled pilot study aims at evaluating the performance of pVNS treatment, using a small wearable stimulation device (AuriMod CT01), comparing personalized and non-personalized stimulation paradigms in patients with chronic low-back pain. Patients will be randomized in one of the following treatment groups (1) Group A: Stimulation with personalized stimulation parameters and amplitude, (2) Group B: Stimulation with personalized stimulation amplitude, (3) Group C: Stimulation without personalization (comparator group). Patients will be treated for 8 weeks. Patients will receive standardized pain medication including rescue medication in parallel. An additional follow-up period of 12 weeks allows to evaluate sustainable and late-time effects of treatment. Patients will use a therapy management system to monitor outcome.

Official Title
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Personalized Auricular Vagus Nerve Stimulation in Patients With Intractable Chronic Low Back Pain: A Randomized Controlled Pilot Study

Conditions
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Chronic Low-back Pain

Intervention / Treatment
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* Device: AuriMod CT01_A
* Device: AuriMod CT01_B
* Device: AuriMod CT01_C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 to 65 years at screening Patient has an understanding of the study and its procedures, agrees to its provisions, and gives written informed consent prior to any study-related procedures Chronic back pain with or without leg pain (CBLP) persisting for at least 3 months A minimum of 70 (out of 180) points on the Computer User Self-Efficacy Scale at the screening visit Patient is constant with respect to pain treatment during the screening phase A daily average VAS >= 4 on at least half of the days in the screening phase Compliance with the daily status reporting requirements as demonstrated by having valid required data entries for all days. It is acceptable if data of one day is missing in the screening phase Exclusion Criteria: Patients with age under 18 Hemophilia Infection, eczema, or psoriasis at application site Numbed and desensitized skin at the application site Florid malignant diseases Mental and physical impairments that represent a source of risk for handling the device The presence of a cardiac pacemaker, defibrillator, cochlear implant, or other active implantable device Vagal hypersensitivity Indication for back surgery High-grade spinal stenosis Patients with other active implants Patients with autonomic disorders Patients with diabetes type I or II Patients taking Beta-Blockers Patients taking drugs carrying the potential risk of arrhythmia (tricyclic medications, Alzheimer drugs, etc.) Clinically significant hip or knee arthritis Allergy against rescue medication used during the study History of Vagus Nerve Stimulation Pregnant or nursing female patients Patients with arrhythmia, bradycardia, other rhythm disorders or any other clinically significant cardiac anomalies detected during ECG at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Personalized stimulation parameters and amplitude | Device: AuriMod CT01_A<br>* AuriMod CT01 is a wearable medical device for personalised pain treatment through auricular vagus nerve stimulation. AuriMod CT01 is a battery-operated electrical stimulation device, to be placed behind the ear on the neck. AuriMod CT01 connects to three needle electrodes, which are placed in vagally innervated regions of the auricle. It emits electrical signals with a personalized set of stimulation parameters and adjustable amplitude.<br>|
| Experimental: Group B<br>Personalized stimulation amplitude | Device: AuriMod CT01_B<br>* AuriMod CT01 with a fixed set of stimulation parameters and adjustable stimulation amplitude.<br>|
| Active Comparator: Group C<br>Non-personalized stimulation | Device: AuriMod CT01_C<br>* AuriMod CT01 with a fixed set of stimulation parameters and amplitude.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average VAS | Change from baseline to End of Treatment (EoT) in average Visual Analogue Scale (VAS; scale 0-10, steps 0.1, 0...no pain, 10...worst pain) during the last 24 hours before the visit | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Max/Min VAS | Change from baseline to EoT in max/min VAS (scale 0-10, steps 0.1, 0...no pain, 10...worst pain) | 8 weeks | 
| Average/Max/Min VAS (follow-up; scale 0-10, steps 0.1, 0...no pain, 10...worst pain) | Change from baseline to End of Follow-Up in average/max/min VAS | 20 weeks | 
| Normalized average/max/min VAS (scale 0-10, steps 0.1, 0...no pain, 10...worst pain) | Baseline-adjusted area under the max/min/average VAS from baseline to EoT | 8 weeks | 
| VAS (follow-up; scale 0-10, steps 0.1, 0...no pain, 10...worst pain) | VAS during follow-up | 12 weeks | 
| Medication use | Pain and rescue medication consumption during treatment and follow-up phase | 20 weeks | 
| Heart Rate | Change in heart rate over therapy and follow-up | 20 weeks | 
| Heart Rate Variability | Change in heart rate variability over therapy and follow-up | 20 weeks | 
| Blood Pressure | Change in blood pressure over therapy and follow-up | 20 weeks | 
| Patient motility | Change in daily step count over therapy and follow-up | 20 weeks | 
| painDETECT | painDETECT questionnaire over treatment and follow-up | 20 weeks | 
| EQ-5D-5L | EQ-5D-5L questionnaire over treatment and follow-up | 20 weeks | 
| HADS | Hospital Anxiety and Depression Score (HADS) over treatment and follow-up | 20 weeks | 
| Sleep quality | Sleep quality (5-item questionnaire) over treatment and follow-up | 20 weeks | 
| Wellbeing | Subjective wellbeing (on a 3-point ordinal scale: good, medium, bad) | 20 weeks | 
| Perception Scale | AuriMod CT01 Perception Scale evaluating the quality of stimulation perception in a 10-item questionnaire at EoT | 8 weeks | 
| Usability Scale | AuriMod CT01 Usability scoring using the System Usability Scale (10-item scale from 10-50, 10...worst usability, 50...best usability) at EoT | 8 weeks | 
| Socioeconomic data | Socioeconomic data change over treatment and follow-up | 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vagus Nerve Stimulation, Personalization, Therapy Management