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

NCT05543239 | Unknown

• 1 other identifier: 20220901
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Neuropathic Pain; Radiotherapy Side Effect

Keywords

Radiotherapy-Related Neuropathic Pain; Transcutaneous Auricular Vagus Nerve Stimulation; Head and Neck Cancers; Randomized controlled trials

Outcome Measures

Primary Outcomes (1)

• Change from baseline to day 7 with respect to pain intensity based on the NRS.

  The primary outcome of this trial is to evaluate the change from baseline to Day 7 with respect to pain intensity based on the NRS, which evaluates the average pain in the last 24 hours from "0" indicating "No Pain" to "10" indicating "Pain as bad as you can imagine".

  Day 7

Secondary Outcomes (8)

• Change from baseline to week 16 with respect to pain intensity based on the NRS.

  week 16

• BPI-SF

  day 7, week 16

• POMS-SF

  day 7, week 16

• WHOQOL-BREF

  day 7, week 16

• FACIT-F

  day 7, week 16

Study Arms (2)

TaVNS

ACTIVE COMPARATOR

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.

Device: Transcutaneous Auricular Vagus Nerve Stimulation(TaVNS)

Sham TaVNS

SHAM COMPARATOR

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.

Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation(SS)

Interventions

Transcutaneous Auricular Vagus Nerve Stimulation(TaVNS) DEVICE

Transcutaneous Auricular Vagus Nerve Stimulation (TaVNS) works by stimulating the auricular branches of the vagus nerve (mainly distributed in the concha cavity and conchae) through electrical impulses.Electrodes were placed on the concha of the left ear after cleaning the skin of the concha with a small disposable alcohol pad. Stimulation pulses (frequency 30 Hz, pulse width 300 us) were generated by TaVNS device, the amplitude was increased within 30 seconds to the subject produced a tingling sensation, and then descend within 15 seconds to the maximum tolerable amount without pain. Inform the subject that "target stimulus has been reached", then stimulate for 30 minutes.

TaVNS

Sham Transcutaneous Auricular Vagus Nerve Stimulation(SS) DEVICE

Place electrodes on the concha of the left ear after cleaning the skin of the concha with a small disposable alcohol pad. The same stimulation pulses (30 Hz frequency, 300 us pulse width) were generated by the same device, the amplitude was increased within 30 seconds to the subject produced a tingling sensation, and then ramps down to zero stimulus over 15 seconds. The subjects were told that "the target stimulus has been reached". Patients receive sham stimulation for 30minutes.

Sham TaVNS

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged ≥18 years with an estimated survival of at least 5 months;
• Prior radiotherapy for histologically confirmed cancer ≥ 6 months prior to study entry;
• 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;
• 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.

You may not qualify if:

• Current diagnosis of tumor recurrence or metastasis and evidence of tumor-associated pain;
• Patients with non-radiotherapy induced neuropathic pain, e.g. postherpetic neuralgia, diabetes mellitus, HIV infection, spinal cord injury and other neurological disease;
• Use of carbamazepine, gabapentin, pregabalin, TaVNS or transcranial magnetic stimulation within the last 30 days prior to study entry;
• 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;
• Concomitant medication that may cause an adverse interaction with pregabalin, including sedative (e.g., benzodiazepines);
• Significant renal impairment: plasma creatinine\>1.5mg/ml, creatinine clearance \< 60 mL/min;
• History of anaphylactic response to pregabalin;
• 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;
• Patients with cardiac pacemakers or implanted ECG monitoring equipment;
• Evidence of severe systemic diseases;
• Subjects with any other condition which, in the investigator's judgment might interfere the outcome of the study;
• Refuse to provide written informed consent;
• Cognitive function and language skills are insufficient to complete study questionnaires;
• Pregnant or lactating women.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (4)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510120, China

RECRUITING

Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center

Guangzhou, 510060, China

NOT YET RECRUITING

Department of Nasopharyngeal Carcinoma, The Affiliated Cancer Hospital and Institute of Guangzhou Medical University

Guangzhou, 510080, China

NOT YET RECRUITING

Department of Neurology, The Affiliated Brain Hospital of Guangzhou Medical University

Guangzhou, 510450, China

NOT YET RECRUITING

Related Publications (2)

• Zuo X, Xu Y, Li S, Jiang J, Wang J, Zhu Y, Pan D, Li H, Chen Y, Chen Y, Rong X, Zheng D, Lu K, Mai H, Chen M, Chen P, Li J, Simone CB, Chua MLK, Li Y, Shen Q, Xiao S, Tang Y. Efficacy and safety of transcutaneous auricular vagus nerve stimulation plus pregabalin for radiotherapy-related neuropathic pain in patients with head and neck cancer (RELAX): a phase 2 randomised trial. EClinicalMedicine. 2025 Jul 12;86:103345. doi: 10.1016/j.eclinm.2025.103345. eCollection 2025 Aug.

  PMID: 40697962 DERIVED

• Zuo X, Li Y, Rong X, Yang X, Zhu Y, Pan D, Li H, Shen QY, Tang Y. Efficacy of transcutaneous auricular vagus nerve stimulation on radiotherapy-related neuropathic pain in patients with head and neck cancers (RELAX): protocol for a multicentre, randomised, double-blind, sham-controlled trial. BMJ Open. 2023 Sep 20;13(9):e072724. doi: 10.1136/bmjopen-2023-072724.

  PMID: 37730386 DERIVED

MeSH Terms

Conditions

Neuralgia; Radiation Injuries; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Neoplasms by Site; Neoplasms

Study Officials

• Yamei Tang, M.D.;PHD.

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yamei Tang, M.D.;PHD.

CONTACT

+86-020-34070569; tangym@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: An independent physiotherapist performs vagus nerve stimulation or sham stimulation according to the group envelope; Investigators (physicians) are only responsible for administering medications other than vagus nerve stimulation;Before treatment, all subjects were told that the intensity of this treatment method may not be felt; The therapeutic device is placed in an opaque airtight pouch that is invisible to both the clinician and the patient during use. The control strategy used "transient sham stimulation", which allows for subjects blinding while delivering a true placebo treatment. Data analysts will be blinded to the allocated treatment group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 16, 2022
• Study Start: September 16, 2022
• Primary Completion: November 1, 2023
• Study Completion: March 1, 2024
• Last Updated: October 12, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)