Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation on Radiotherapy-Related Neuropathic Pain (RELAX)

Sun Yat-sen University

Status: Enrolling

Conditions: Radiotherapy Side Effect; Neuropathic Pain

Treatments: Device: Transcutaneous Auricular Vagus Nerve Stimulation(TaVNS); Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation(SS)

Study type: Interventional

Funder types: Other

Identifiers

NCT05543239

20220901

Details and patient eligibility

About

This multi-center, randomized, double-blind, sham-controlled trial aims to investigate the effect and safety of TaVNS in treating radiotherapy-related neuropathic pain.

Full description

Radiotherapy-related neuropathic pain(RRNP) is one of the most distressing complications after radiotherapy for head and neck cancers. The prevalence of neuropathic pain in cancer pain patients is as high as 31-45%.Our previous RCT of pregabalin for RRNP showed that nearly 41.6% of patients still did not achieve 30% pain relief even with standard doses of pregabalin. At the same time, drug side effects such as dizziness and obesity are common, and a dose titration process for at least one week is required.Therefore, new treatments that effectively relieve pain and improve quality of life must be explored.

Transcutaneous Auricular Vagus Nerve Stimulation (TaVNS) works by stimulating the auricular branches of the vagus nerve through electrical impulses. Previous studies have shown it can relieve various pains including migraine, cluster headache, musculoskeletal pain with few adverse events. This study plans to evaluate the efficacy of TaVNS versus sham stimulation for relieving RRNP, and assessed its safety.

Enrollment: 116 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female patients aged ≥18 years with an estimated survival of at least 5 months;
2. Prior radiotherapy for histologically confirmed cancer ≥ 6 months prior to study entry;
3. Pain for at least 4 weeks with an average intensity of ≥ 4 on an 11-point numeric rating scale (NRS) in the run-in period, and pain locations in accordance with radiated innervated areas, e.g. head, face, neck and arms;
4. Neuropathic pain defined according to clinical history, symptoms, physical signs, and a score ≥ 12 in the Chinese version of Leeds Assessment of Neuropathic Symptoms and Signs questionnaire (LANSS) by two trained and experienced neurology specialists.

Exclusion criteria

1. Current diagnosis of tumor recurrence or metastasis and evidence of tumor-associated pain;
2. Patients with non-radiotherapy induced neuropathic pain, e.g. postherpetic neuralgia, diabetes mellitus, HIV infection, spinal cord injury and other neurological disease;
3. Use of carbamazepine, gabapentin, pregabalin, TaVNS or transcranial magnetic stimulation within the last 30 days prior to study entry;
4. Other ongoing treatment for neuropathic pain, including antidepressants with norepinephrine and serotonin reuptake inhibition, calcium channel α2-δ ligands and other anticonvulsant medications, and topical lidocaine;
5. Concomitant medication that may cause an adverse interaction with pregabalin, including sedative (e.g., benzodiazepines);
6. Significant renal impairment: plasma creatinine>1.5mg/ml, creatinine clearance < 60 mL/min;
7. History of anaphylactic response to pregabalin;
8. Ulceration of the auricle skin; Diagnosis of mental illness, peptic ulcer,AV III degree block, heart rate< 50/min, heart rate corrected QT interval > 450ms;
9. Patients with cardiac pacemakers or implanted ECG monitoring equipment;
10. Evidence of severe systemic diseases;
11. Subjects with any other condition which, in the investigator's judgment might interfere the outcome of the study;
12. Refuse to provide written informed consent;
13. Cognitive function and language skills are insufficient to complete study questionnaires;
14. Pregnant or lactating women.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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116 participants in 2 patient groups

TaVNS

Active Comparator group

Description:

Patients will receive TaVNS stimulation for 30 minutes, twice a day (between 9:00 to 10:00 and 15:00 to 16:00), for 7 consecutive days. Stimulation pulses (30 Hz frequency, 300 μs pulse width) were generated by a commercial transcutaneous auricular vagus nerve stimulation unit (tVNS 501，Jiangsu, China), and the amplitude was increased to the maximum amount tolerated by the subject without pain, then stimulate for 30 min. All subjects were told that they may or may not feel any sensation from the stimulation, and the unit is packed in an opaque bag throughout the treatment.

Treatment:

Device: Transcutaneous Auricular Vagus Nerve Stimulation(TaVNS)

Sham TaVNS

Sham Comparator group

Description:

Patients will receive sham TaVNS stimulation for 30 minutes, twice a day (between 9:00 to 10:00 and 15:00 to 16:00), for 7 consecutive days. Stimulation unit was active for the first 30s, stimulation pulses (30 Hz frequency, 300 μs pulse width) were generated by a commercial transcutaneous auricular vagus nerve stimulation unit (tVNS 501，Jiangsu, China).Then dropped to zero stimulation during 15s and shut down. All subjects were told that they may or may not feel any sensation from the stimulation, and the unit is packed in an opaque bag throughout the treatment.

Treatment:

Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation(SS)