Vagus Nerve Stimulation for epilepsy in children and adults: Assessment of Longer term clinical and cost Effectiveness in a Randomised controlled Trial (VNS-ALERT)
A small electrical generator implanted just below the collarbone sends pulses to the vagus nerve in an attempt to reduce seizures—but after decades of use in the NHS, no one has rigorously tested whether it actually works over the long term, especially in children and people with intellectual disabilities. This matters because vagus nerve stimulation (VNS) is widely offered to people with drug-resistant epilepsy who cannot have brain surgery, yet the evidence behind it is weak. The trial will randomly assign 50% of participants to immediate VNS activation and the other half to delayed activation after 6 or 12 months, allowing a clean comparison. It will track seizure-free days, quality of life, caregiver burden, costs, and side effects for up to six years. A nested qualitative study will also explore why recruitment is difficult for people with intellectual disabilities and how to improve it. If VNS proves effective and cost-effective, the NHS could confidently expand access to a treatment currently supported by thin evidence. If it does not, the health service could redirect resources toward therapies that work. Either way, clinicians and families will finally have data to guide decisions about a device that alters brain activity every day.
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Background: Vagus nerve stimulation (VNS) involves electrical stimulation to the left vagus nerve from a small generator placed subcutaneously just below the left clavicle. The principal aim of the VNS is to reduce seizure burden (frequency and severity) and improve quality of life. It has become widely used in the NHS for people with treatment refractory epilepsy, but the evidence for its use is weak, particularly for children and for people with complex epilepsy and intellectual disability. Aim: to undertake a longer term RCT that will answer the following questions: 1. What is the clinical effectiveness of VNS versus no VNS at 6 and 12 months in people aged 5 years and over with drug refractory epilepsy? 2. What is the cost effectiveness of VNS versus no VNS in people aged 5 years and over with drug refractory epilepsy? 3. What is the clinical effectiveness of VNS versus no VNS at 6 and 12 months in people aged 5 years and over with drug refractory epilepsy associated with intellectual disability? 4. What is the longer-term clinical effectiveness (beyond 2 years) of VNS? 5. How does the clinical effectiveness of VNS change over time during longer term follow up? 6. What are the experiences and views of patients and their significant others regarding VNS treatment, including how it was used, barriers to use, and opportunities to support use? 7. What are the barriers to recruitment in trials like VNS-Alert, especially for individuals with intellectual disabilities, and what potential solutions can be identified? Methods: Design: Pragmatic, parallel group, un-blinded randomised controlled trial comparing: (A) VNS insertion and immediate activation (50% of participants) (B) VNS insertion and then activation after 6 months (25% of participants) (C) VNS insertion and then activation after 12 months (25% of participants) Participants will be accrued and randomised over 4 years then followed up for a minimum of 2 years (maximum of 6 years). Inclusion criteria: 1. Aged 5 years or older with treatment refractory focal, generalised or unclassified epilepsy; 2. With or without intellectual disability; 3. Not suitable for or does not want a surgical brain resection, or has had a resection that failed; 4. Epilepsy surgery MDT agrees that VNS should be offered as a treatment for epilepsy. Outcome measures: Primary clinical: Seizure free days at 6 months post randomisation. Primary economic: Incremental cost per QALY gained from the perspective of the NHS and Personal Social Services Secondary outcomes: Seizure frequency Seizure severity Episodes of status epilepticus requiring rescue medication, emergency department attendance or hospital admission Adverse effects Mortality Symptoms of depression (6, 12, 18, 24, 36, 48, 60 months) Quality of life of person with epilepsy (6, 12, 18, 24, 36, 48, 60 months) Care giver burden (6, 12, 18, 24, 36, 48, 60 months) Utility measures (baseline, 6, 12, 18, 24, 36, 48, 60 months) Resource use and cost (baseline, 6, 12, 18, 24, 36, 48, 60 months) Nested qualitative study will be embedded within the trial to enhance trial design and conduct and understanding of VNS treatment for people with epilepsy. Timelines: Set up (sponsorship, HRA, ethics) – months 0 to 6 Pilot – months 6 to 24 (assuming 2-month baseline and 12 months randomisation) Cohort recruitment and randomisation – months 6 to 53 Cohort follow up after closing randomisation – months 54 to 77 Analysis and report – months 78 to 84
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