Proof of Concept Study of Vagus Nerve Stimulation
|ClinicalTrials.gov Identifier: NCT03689621|
Recruitment Status : Completed
First Posted : September 28, 2018
Last Update Posted : April 17, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Transcutaneous Vagal Nerve Stimulation (tVNS) Prader-Willi Syndrome||Device: Transcutaneous vagus nerve stimulation (tVNS)||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||January 1, 2016|
|Actual Primary Completion Date :||December 31, 2018|
|Actual Study Completion Date :||December 31, 2018|
Active Comparator: Transcutaneous vagal nerve stimulation (tVNS)
tVNS administered for 4 hours each day and behaviour is recorded.
Device: Transcutaneous vagus nerve stimulation (tVNS)
Placebo Comparator: Baseline
tVNS worn but not switched on whilst collecting behavioural data.
Device: Transcutaneous vagus nerve stimulation (tVNS)
- The number of operationally defined outbursts [ Time Frame: 15-17 months ]Measured using participant and informant diaries.
- The Challenging Behaviour Checklist [ Time Frame: 15-17 months ]Scores on rating scale, repeated over time. Score range 50-55. higher score indicates more severe behaviour.
- Repetitive Behaviour Questionnaire [ Time Frame: 15-17 months ]Scores on rating scale, repeated over time. Total scores range between 20-60. The higher toe score the worse behaviours are.
- Life Experiences Checklist. [ Time Frame: 15-17 months ]Intended to gather information about the potentially traumatic experiences a person has experienced. There is no formal scoring protocol or interpretation per se, other than identifying whether a person has experienced one or more of the events listed. Respondents indicate varying levels of exposure to each type of potentially traumatic event included on a 6-point nominal scale, and respondents may endorse multiple levels of exposure to the same trauma type.
- fMRI at resting and on-task [ Time Frame: 15-17 months ]FMRI data will be analysed using both 1st and 2nd level general linear model (GLM) analyses to compare within cases and across time points. Network analyses of functional connectivity may also be appropriate
- Participants response to challenge [ Time Frame: 15-17 months ]Using methodology developed by Prof Oliver, filmed and subsequently rated blind for emotional and behavioural changes.
- Semi-structured interviews [ Time Frame: 15-17 months ]With participants and carers to probe about any observed subtle changes in behaviour. Analysed thematically.
- Attention shifting ability [ Time Frame: 15-17 months ]Tested via go-no-go task developed for people with PWS by Woodcock et al (2009). Reaction times analysed.
- Salival cortisol measures [ Time Frame: 15-17 months ]recorded across the course of four separate days during the course of study (at waking, 30 minutes post-waking, 45 minutes post-waking, 1 hour post-waking and then four more times throughout the day at approximately +3h, +6h, +9h and +14h after waking).
- Vocal prosody [ Time Frame: 15-17 months ]Two voice recordings of the participant talking will be collected on each of these occasions. Each recording will be at least 20 seconds long, with the participant asked to talk about a positive experience (e.g. favourite birthday, best friend etc.) in one, a less positive time (e.g. a time when he/she was disappointed or sad) in the other. These will be analysed for changes in vocal prosody with t-VNS.
- Heart Rate Variability [ Time Frame: 15-17 months ]derived from ECG and respiration measured using an Intelesens (Belfast) 3-axis 'Zensor' wearable monitor. For each participant ECG recording will take place in 24-hour blocks. HRV will be determined from R-R intervals as root mean of squared successive differences and average HRV will be determined for each participant for brief (15 minutes) and prolonged (24 hours) periods.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03689621
|Principal Investigator:||Tony Holland, Prof.||University of Cambridge|