Clinical trial NCT05543239: Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation on Radiotherapy-Related Neuropathic Pain
Official title: Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation on Radiotherapy-Related Neuropathic Pain in Patients With Head and Neck Cancers: A Multi-center, Randomized, Double-Blind, Sham-Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Neuropathic Pain
Radiotherapy Side Effect
Keywords: Radiotherapy-Related Neuropathic Pain
Transcutaneous Auricular Vagus Nerve Stimulation
Head and Neck Cancers
Randomized controlled trials
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2022-09-16
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline to day 7 with respect to pain intensity based on the NRS.
timeFrame: Day 7
Secondary outcomes:
measure: Change from baseline to week 16 with respect to pain intensity based on the NRS.
timeFrame: week 16
measure: BPI-SF
timeFrame: day 7, week 16
measure: POMS-SF
timeFrame: day 7, week 16
measure: WHOQOL-BREF
timeFrame: day 7, week 16
measure: FACIT-F
timeFrame: day 7, week 16
measure: PGIC
timeFrame: day 7, week 16
measure: CGIC
timeFrame: day 7, week 16
measure: Serum Inflammatory Factors
timeFrame: day 7
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center
city: Guangzhou
country: China
facility: Department of Nasopharyngeal Carcinoma, The Affiliated Cancer Hospital and Institute of Guangzhou Medical University
city: Guangzhou
country: China
facility: Department of Neurology, The Affiliated Brain Hospital of Guangzhou Medical University
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Yamei Tang, M.D.;PHD.
role: PRINCIPAL_INVESTIGATOR
References: