Proof of Concept Study of Vagus Nerve Stimulation Using an External Device for the Treatment of Behaviour Problems in People With Neurodevelopmental Disorders, Specifically Prader Willi Syndrome

The investigator's recent pilot study of vagus nerve stimulation (VNS) from a surgically implanted medical device to control the excess eating behaviour characteristic of Prader-Willi Syndrome (PWS) found that it was safe and acceptable. In addition, there were unanticipated marked improvements in rates of problem behaviours, such as emotional disturbances and verbal and physical outbursts. These observations indicated the need for a trial specifically focusing on the effects of VNS on problem behaviour and also that the use of VNS might be extended to include people with other neurodevelopmental disorders, such as autism spectrum conditions (ASC). The primary aims of this study are: a) to investigate whether VNS, now given by an external medical device, is associated with a significant reduction in the number and severity of maladaptive behaviours in adults with PWS; and b) to undertake a pilot study that includes others with a different neurodevelopmental syndrome who have histories of similar behaviours.

The study will be a single case cross-over design with 4 to 6 months baseline phase and a similar period of active treatment. The study cannot be blind as the stimulation is apparent but the participants will wear the device initially for four hours a day, at times convenient to them, with it switched off in the baseline phase and activated, according to standard protocols, in the treatment phase. Six adults with PWS and six with a different neurodevelopmental disorder with histories of significant problem behaviours will be included initially, with a view to extending if the analysis indicates a likely effect. Behaviours will be operationally defined and measured over time using participant and informant diaries with additional secondary outcome measures. Before and during the treatment phases autonomic nervous system and brain biomarkers will be assessed using ambulatory monitoring of heart rate variability and fMRI brain scans.