University of Liverpool researchers have begun work on a major £2.7 million National Institute for Health and Care Research (NIHR)-funded trial investigating the long-term effectiveness of vagus nerve stimulation (VNS) in people with drug-resistant epilepsy.
The seven-year project, Vagus Nerve Stimulation for epilepsy in children and adults: Assessment of Longer term clinical and cost Effectiveness in a Randomised controlled Trial (VNS-ALERT), is led by Professor Tony Marson, a leading expert in epilepsy at the University of Liverpool.
Epilepsy affects over 600,000 people in the UK. For around a third of these individuals, medication is not effective, leading to drug-resistant epilepsy—a condition that can significantly impair quality of life and increase the risk of premature death. While brain surgery is an option, it is only suitable for a limited number of people and has variable long-term outcomes.
VNS—a treatment involving a small implanted device that sends electrical impulses to the brain via the vagus nerve—offers an alternative for people for whom surgery is not appropriate or has failed. Though VNS is approved for use in the NHS, its long-term clinical and cost effectiveness remains uncertain, particularly for children and individuals with intellectual disabilities, who represent half of all VNS recipients.
The VNS-ALERT trial will recruit 300 participants aged five and above from epilepsy surgery centres across the UK. Participants will be randomly assigned to receive VNS activated immediately, after six months, or after twelve months. The trial’s primary outcome will be the number of seizure-free days experienced by participants, with other outcomes including quality of life, seizure severity, adverse effects, mortality, and cost-effectiveness.
Professor Marson said: “This landmark trial will provide much-needed evidence on whether VNS is a truly effective and cost-efficient treatment for people living with drug-resistant epilepsy. Crucially, we are including children and adults with intellectual disabilities—groups historically underrepresented in epilepsy research.”
Professor Carrol Gamble said “We are excited to be collaborating with Professor Marson on this research which allows us to contribute our extensive expertise in neurological trials in adults and children. We look forward to answering this important clinical question to benefit patients and their families.”
Patient and public involvement has been central to the design and development of the trial. The project was co-designed with a public co-applicant with lived experience of epilepsy, alongside contributions from the Epilepsy Research Institute and the Shape Network—the UK’s largest community of people affected by epilepsy. Early feedback from surveys and workshops directly informed trial design, including the decision to use a staggered activation model to ensure all participants receive a VNS device.
Throughout the trial, public contributors will remain actively involved through advisory groups and representation on the project’s steering committee. A qualitative sub-study will also explore participants’ experiences, helping researchers ensure the trial remains inclusive and responsive to the needs of those taking part.
The trial will be delivered by Liverpool Clinical Trials Centre and other collaborators include the Walton Centre NHS Foundation Trust, North Bristol NHS Trust, Bangor University, University Hospital of Wales, University of Plymouth, Oxford University Hospitals NHS Foundation Trust, the University of Sheffield and Newcastle University.
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About the University of Liverpool
Founded in 1881 as the original ‘red brick’, the University of Liverpool is one of the UK’s leading research-intensive higher education institutions with an annual turnover of £675.1 million, including an annual research income of £160.6 million.
Now ranked in the top 150 universities worldwide (QS World Rankings 2026), we are a member of the prestigious Russell Group of the UK’s leading research universities and have a global reach and influence that reflects our academic heritage as one of the country’s largest civic institutions.
The latest UK rankings of circa 130 institutions have placed the University of Liverpool at 23rd (Times and Sunday Times Good University Guide 2025), 27th (2025 Guardian University Guide), 25th (Daily Mail University Guide 2025) and 23rd (2026 Complete University Guide) nationally.
NIHR
The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research.
We do this by:
- funding high quality, timely research that benefits the NHS, public health and social care
- investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services
- partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research
- attracting, training and supporting the best researchers to tackle complex health and social care challenges
- collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system
- funding applied global health research and training to meet the needs of the poorest people in low and middle income countries
NIHR is funded by the Department of Health and Social Care.
Our work in low and middle income countries is principally funded through UK international development funding from the UK government.