Use of taVNS for Painful Diabetic Neuropathy: 12-Week Randomized, Sham-Controlled Trial

Ki vehet részt

• Age 30-70 years. Type 2 diabetes mellitus diagnosed ≥ 1 year
• Painful distal symmetric polyneuropathy ≥ 3 months, meeting all:
• DN4 score ≥4; Average daily pain NRS ≥4 during a 7-day run-in; Clinical examination consistent with DPN (e.g., reduced vibration or abnormal monofilament, or neuropathy disability score >0)
• Stable antidiabetic regimen and neuropathic-pain medications for ≥4 weeks before randomization, with no planned changes during the 12-week treatment unless medically necessary
• Biomarker enrichment: at least one of the following at screening:
• hs-CRP ≥2.0 mg/L or IL-6 above laboratory median; or Reduced heart-rate variability (e.g., RMSSD at or below the age/sex-adjusted 25th percentile) on standardized 5-minute ECG
• Able to use the ear-clip device and the study smartphone app (or willing to use a study phone), and to attend baseline, Week 6 and Week 12 visits (including corneal confocal microscopy and finger-prick sampling)
• Provides written informed consent

Ki nem vehet részt

• Implanted electronic medical devices (e.g., pacemaker, ICD, deep brain stimulator, cochlear implant) or other contraindication to transcutaneous electrical stimulation
• Current systemic immunosuppressive therapy (e.g., ≥10 mg/day prednisone equivalent or biologic agents) or expected to start during the trial
• Initiation/change of neuromodulation treatments for pain within 3 months or prior taVNS use within 3 months
• Peripheral neuropathy not due to diabetes (e.g., vitamin B12 deficiency, hypothyroidism, uremia/CKD-related, chemotherapy-induced, HIV, hereditary neuropathies), or predominant radiculopathy/entrapment neuropathy
• History of epilepsy/seizure disorder, clinically significant arrhythmia, or unexplained syncope within 6 months
• Unstable cardiovascular disease within 3 months (e.g., acute coronary syndrome, decompensated heart failure)
• Corneal disease precluding CCM (e.g., active keratitis) or inability to undergo CCM imaging
• Uncontrolled psychiatric illness (including active suicidal ideation) or cognitive impairment limiting consent/compliance
• Pregnant or breastfeeding, or planning pregnancy during the study. Any condition or circumstance that, in the investigator's judgment, would interfere with safe participation or with study assessments
• Severe renal impairment (eGFR <30 mL/min/1.73 m²) or on dialysis. Active diabetic foot ulcer Grade ≥2, active systemic infection, or dermatologic disease at the ear-clip site