ReVita: home-based transcutaneous auricular vagus nerve stimulation for reducing pathological fatigue in chronic neurological and post-infectious conditions—study protocol for a randomized, double-blind, sham-controlled trial

Abstract

Abstract Background Pathological fatigue is one of the most prevalent and disabling symptoms across chronic neurological, post-infectious, and inflammatory diseases, yet effective treatments remain limited. Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe, non-invasive neuromodulatory intervention that targets neuroimmune and autonomic pathways implicated in the development and persistence of fatigue. This randomized controlled trial investigates whether home-based taVNS can reduce fatigue severity in a transdiagnostic population. Methods This study is a randomized, double-blind, sham-controlled, parallel-group clinical trial conducted at the University Hospital Magdeburg. Eligible adult participants (≥ 18 years) with clinically significant chronic fatigue from two diagnostic clusters (neurological disorders and post-infectious syndromes) will be enrolled and randomized (1:1) to receive either active taVNS or sham stimulation for 4 weeks. Stimulation is self-administered at home twice daily for 30 min. The primary outcome is change in fatigue severity from baseline to the end of the intervention, assessed using the Modified Fatigue Impact Scale (MFIS). Secondary outcomes include quality of life (WHOQOL-BREF), depressive symptoms (BDI-II), daytime sleepiness (ESS), cognitive performance (SDMT and TAP subtest alertness), neurophysiological markers (resting-state EEG and P50 sensory gating) and HRV indices (Garmin Vivosmart 5). Blinding integrity will be assessed at study end. Data will be analyzed according to an intention-to-treat framework. No interim analyses are planned. Adverse events will be monitored continuously. Discussion This is to be the first transdiagnostic study to evaluate home-based taVNS as a potential therapeutic approach for pathological fatigue across multiple chronic disease groups. The combination of rigorous blinding, digital monitoring, and parallel assessment of clinical and physiological parameters allows for an in-depth evaluation of both treatment effectiveness and mechanistic correlates. If successful, taVNS could offer a scalable and accessible intervention for a large and underserved patient population. Trial registration The trial was registered in the German Clinical Trials Register (DRKS) under the identification number DRKS00038292. Registered on December 01, 2025. URL: https://drks.de/search/de/trial/DRKS00038292 .