A Pilot Study to Evaluate Safety and Ability of the Transcutaneous Auricular Vagus Nerve Stimulator the Travagus One System to Decrease Inflammatory Mediators in Patients With Duchenne Muscular Dystrophy.

Purpose and aim:

The overall aim is to investigate efficacy and safety of a newly developed non-invasive, auricular, investigational equipment named the TRAVAGUS ONE System that electrically stimulates the auricular branch of the vagus nerve to activate the cholinergic anti-inflammatory mechanism to study possible inhibiting effects on increased levels of systemic inflammatory mediators in DMD patients. The mode of treatment is termed transcutaneous auricular vagus nerve stimulation (taVNS). Specifically, we will address the following research questions:

1. Can taVNS treatment for a week reduce systemic levels of inflammatory molecules?
2. What is the safety profile of taVNS? Survey of the field Several thousand children with epilepsy have over the past 10 years been treated with invasive or external taVNS therapy with no or mild adverse effects. There is a clinical need for improved anti-inflammatory therapy with less serious adverse effects in DMD. The aim of our planned study is to investigate whether taVNS treatment via the cholinergic anti-inflammatory mechanism may reduce systemic levels of inflammatory molecules involved in the pathogenesis of DMD. If so, that would motivate future extended therapeutic taVNS studies in DMD patients. Therapy using taVNS is based on non-invasive activation of the endogenous cholinergic anti-inflammatory pathway, a mechanism discovered by Kevin Tracey, one of the founders of taVNS AB, which is the sponsoring company of the present clinical investigation. The cholinergic anti-inflammatory pathway is the efferent part of the inflammatory reflex, a neural circuit that counteracts exaggerated dysfunctional inflammatory responses. The anti-inflammatory effects are mediated via acetylcholine released via the vagus system and a subset of mobile T lymphocytes (T ChAT-cells) capable of acetylcholine synthesis. These anti-inflammatory T cells operate both within and outside compartments innervated by the vagus system. Alpha-7 nicotinic acetylcholine receptors (alpha-7nAChR) respond to acetylcholine by guiding activities downregulating proinflammatory cytokine synthesis, redirecting the traffic of mobile inflammatory cells, and converting pro-inflammatory macrophages to healing macrophages. Using a surgically implanted vagus nerve stimulator Kevin Tracey and Ulf Andersson (the author of this document) provided the original clinical report in 2012 of successful VNS treatment in a chronic inflammatory disease. Multiple pilot studies using either invasive or external VNS in various inflammatory diseases have supported the validity of the original discovery. FDA approved an implantable vagus nerve stimulating device for treatment of rheumatoid arthritis in July 2025 as a result of a successful randomized, placebo-controlled multicenter study with rheumatoid arthritis patients refractory to conventional therapy.

The auricular branch of the vagus nerve is a sensory nerve to the external ear including the cymba conchae region. Stimulation of this auricular nerve branch delivers afferent neuronal impulses, whereas cervically implanted devices deliver both efferent and afferent vagus nerve stimulation. Extended experience from therapeutic epilepsy studies has provided reassuring safety results regarding taVNS therapy. Functional magnetic resonance imaging demonstrates that taVNS activates the main vagal afferent pathway through the brainstem to upstream cortical projections in a similar way to implanted cervical VNS electrodes, confirming this nerve as a suitable non-invasive target to administer vagus nerve stimulation.

Study design: