CompletedNot Applicable

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

Pakistan185 participantsStarted 2025-01-05

Plain-language summary

This 12-week, randomized, double-blind, sham-controlled, parallel-group trial will evaluate the analgesic and mechanistic effects of home-based transcutaneous auricular vagus nerve stimulation (taVNS) in adults with painful diabetic peripheral neuropathy (DPN). To increase the likelihood of detecting a biological signal, enrollment is biomarker-enriched for low-grade systemic inflammation and autonomic imbalance (e.g., elevated high-sensitivity C-reactive protein/interleukin-6 or reduced heart-rate variability \\\[HRV\]). Participants are randomized 1:1 to active taVNS (ear-clip stimulation, twice daily) or an indistinguishable sham device for 12 weeks; background diabetes and pain therapies are kept stable where possible. Adherence and daily pain ratings are captured via a smartphone application. The primary outcome is change in average daily pain intensity (11-point Numeric Rating Scale) from baseline to Weeks 10-12. Secondary outcomes assess proposed mechanisms of action and include HRV indices, inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein), serum neurofilament light (sNfL) measured from finger-prick dried-spot samples, and corneal confocal microscopy (CCM) metrics of small-fiber integrity (corneal nerve fiber length/density). Additional outcomes include sleep interference, DN4 score, Patient Global Impression of Change, responder rate (≥2-point pain reduction), and safety. The study is multicenter in Pakistan and is designed to test whether taVNS reduces painful symptoms and favorably shifts objective autonomic, inflammatory, and nerve-injury biomarkers, providing scalable evidence relevant to low- and middle-income settings.

Who can participate

Age range

30 Years – 70 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: 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 Exclusion Criteria: 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. Implanted electronic medical devices (e.g., pacemaker, ICD, deep brain stimulator, cochlear implant) or other contraindication to transcutaneous electrical stimulation. History of epilepsy/seizure disorder, clinically significant arrhythmia, or une…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Change in average daily pain intensity (11-point Numeric Rating Scale, NRS 0-10)

Timeframe: Baseline to Week 12 (primary window = Weeks 10-12)

Trial details

NCT IDNCT06292962

SponsorSaima Abass Tahammal

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-05-01

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