Percutaneous Auricular Vagus Nerve Stimulation With Conventional Rehabilitation Training in Chronic Back Pain Patients

Efficacy of Percutaneous Auricular Vagus Nerve Stimulation Combined With Conventional Rehabilitation Training to Improve Functional Outcome in Chronic Back Pain Patients (CURA): A Randomized Controlled Pilot Study

The therapeutic action of aVNS in pain treatment is based on the masking of pain by the electrical stimulation pulses, the activation of inhibiting pain control systems, and the release of neurotransmitters, such as endorphins. Pairing VNS stimulation with exercise and physiotherapy has yielded beneficial results in stroke patients as well as in smaller studies with back pain patients, already in short periods of time (2-4 weeks).

The current study is intended to evaluate the performance of percutaneous auricular Vagus Nerve Stimulation (pVNS) in combination with Standard-of-Care (SoC) in a 3-week in-patient rehabilitation setting, in patients with chronic musculoskeletal/myofascial back pain. This will be a prospective, open, randomized, controlled pilot study to evaluate pVNS using the VIVO® wearable medical device for personalized pain treatment, in terms of feasibility, efficacy, and safety in combination with rehabilitation training. Patients will be randomized into one of the following treatment groups:

• Group A: VIVO® (pVNS) + SoC (treatment group)
• Group B: SoC (control/comparator group) Patients will remain on treatment for 3 weeks. This is comparable to other studies performed earlier, which showed safe and effective use of pVNS in chronic pain patients. The additional follow-up period of 3 weeks (optional 3 months and 6 months) allows to evaluate sustainable effects of treatment and late time effects, as previously shown in other studies.

Patients in the treatment group (VIVO® + SoC) will receive personalized aVNS therapy in combination with SoC. Personalization of VIVO® treatment is performed based on the individual perception level of the stimulation at the ear with regards to the stimulation amplitude (in Group A). Amplitude is adjusted (range 0-5 V) to reach a distinct but comfortable tingling sensation to reach activation of Aβ-fibers of the auricular vagus nerve but not Aδ-fibers producing a sensation of pain. Not only the Investigator is able to adjust the amplitude at the trial visit (via VIVO® Pen) but also the patient is able to adjust the amplitude according to his/her perception.

Patients will be randomized in this pilot study to receive either aVNS with the VIVO® system in addition to SoC vs. SoC alone as comparator group. Estimates of performance endpoints will thus be contrasted between aVNS and an established treatment option in this indication and controlled for regression to the mean and other forms of sampling bias.

All concomitant medication and therapies will be thoroughly documented and taken into account in the final analysis.

Inclusion Criteria:

• Male or female aged ≥30 and ≤65 years
• Indication: chronic myofascial/musculoskeletal back pain
• normal function of spinal nerves
• Intractable pain for more than 6 months
• Patient on oral pharmacotherapy ≤ WHO II with no adequate response or intolerant
• Severity according to "Leistungskategorie 2" of BVAEB classification, which means Barthel Index 35-80, 6-minute walk test 300-480 m OR ergometry 50-80%/0.75-1.25, ICF-Core-Sets grade 3
• Average pain over the last 4 weeks according to painDETECT ≥ 4 and ≤ 9 at baseline
• ODI 20-80 at baseline
• Patient understands the therapy and procedures, agrees to its provisions, and gives written informed consent prior to any procedures

Exclusion Criteria:

• Organic back pain (trauma, fracture, tumor, infection, severe degenerative spine, documented high-grade spinal stenosis, rheumatologic conditions)
• Indication for back surgery
• Radicular pain
• Back surgery within the last 6 months
• New analgesics 2 weeks before baseline (paracetamol, NSAIDs, Metamizol, etc.)
• Opioid analgesic therapy > WHO II
• Underwent other physical therapy modalities for back pain, also TENS, 2 weeks before baseline
• History of vagus nerve stimulation or electrical auricular stimulation
• History of vasovagal syncope
• High BMI > 35 kg/m² (Obesity Class 2 or higher)
• Hemophilia or strong anti-coagulation medication
• Autonomic disorders
• Advanced stage or poorly controlled diabetes mellitus type I or II
• Poorly controlled high blood pressure
• Major psychiatric comorbidity (at the discretion of the PI)
• Other serious clinically relevant co-morbidity
• History of arrhythmia, bradycardia, other rhythm disorders or any other clinically significant cardiac anomalies
• Infection, eczema, or psoriasis at application site (ear and neck)
• Numbed and desensitized skin at the application site (ear and neck)
• Chronic drug or alcohol abuse within the last 6 months
• Pregnant or nursing female patients
• Active implantable device
• Open pension request
• Currently participating in another clinical trial or participated over the last 3 months
• Relevant change in concomitant treatment or medication during the study