Title: Percutaneous Auricular Nerve Stimulation for Treating Post-COVID Fatigue (PAuSing-Post-COVID Fatigue)
Funder: Department of Health and Social Care

Abstract: This study aims to establish whether self-administered non-invasive transcutaneous vagus nerve stimulation can reduce symptoms of post-covid fatigue (pCF) in adults with long covid. Fatigue affects >50% of those with Long COVID. The causes of fatigue appear similar across different conditions, whether chronic immune-mediated diseases such as primary Sj&ouml;gren s syndrome, or post-viral fatigue. We have recently shown that non-invasive vagus nerve stimulation (nVNS) delivered twice daily for 26 days in patients with primary Sj&ouml;gren s syndrome can significantly reduce symptoms of fatigue. VNS might therefore be an effective intervention for post-viral fatigue, specifically pCF. The vagus nerve can be stimulated non-invasively via its auricular branch, which supplies the skin around the ear canal. This can be self-administered using a handheld battery-powered transcutaneous electrical nerve stimulation (TENS) device via a clip electrode attached to the tragus of the ear. Participants diagnosed with COVID19 but not admitted to hospital who develop post-COVID Fatigue (pCF) will be recruited to this study via a trial website and social media. Effects of VNS on pCF will be tested in a randomised double-blind sham-controlled study with three interventional arms: Active nVNS (active clip electrode on tragus; TENS ON); Sham nVNS (inactive clip electrode on tragus; TENS ON); and Active Control (clip electrode on earlobe; TENS ON). TENS will be self-administered by participants in the home. Assessment and testing (neurophysiology, blood biomarkers) will be completed at baseline, 8 weeks and 16 weeks in dedicated laboratories at Newcastle University. Wearable technology will be used to assess day-to-day fatigue-related parameters in the home during the initial 8-week intervention. After 8 weeks all participants will crossover to receive active nVNS.

Lay abstract: Fatigue is a very common symptom of Long COVID. Feedback from patients has highlighted the devastating impact of post-Covid Fatigue (pCF) on lives as well as the need for novel therapeutic options. Interventions that enhance existing therapies and empower those suffering with pCF to manage their own treatment at home are particularly needed. People with the rare disease, primary Sj&ouml;gren s syndrome, also show fatigue. We previously demonstrated in such people that non-invasive vagus nerve stimulation (nVNS) at the neck delivered twice daily for 26 days significantly reduced fatigue symptoms. Here, we will extend this work to test whether nVNS can reduce fatigue in adults with pCF. The vagus nerve has a branch which supplies the skin around the ear canal. Stimulating the ear can be easily and safely self-administered at home using a handheld battery-powered transcutaneous electrical nerve stimulation (TENS) device, available over the counter without prescription. We will focus on people diagnosed with COVID19 but not requiring hospital in-patient treatment. In this study, 96 participants with pCF will be randomly assigned to one of three study groups. One group will asked to stimulate the part of the ear containing the vagus nerve. For comparison, the other two groups will either be asked to stimulate a part of the ear that does not contain the vagus, or given an electrode that is inactive. After 8 weeks, changes in fatigue severity will be measured using questionnaires and wearable technologies. We will also use lab-based tests to measure changes in brain circuits. From week 9, all participants will switch to receive nVNS until week 16 and the above measurements repeated.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: INFECTION