Clinical trial NCT03689621: Proof of Concept Study of Vagus Nerve Stimulation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Transcutaneous Vagal Nerve Stimulation (tVNS)
Prader-Willi Syndrome
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: Foundation for Prader-Willi Research
First posted: 2018-09-28
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Male or female aged over 18 years of age.
* Genetically and clinically determined diagnosis of PWS or meeting clinical or the presence of another neurodevelopmental syndrome such as an autistic spectrum condition.
* History of problem behaviours of, on average, at least one significant informant-reported episode each week.
* Capacity to consent.
* Able to commit to the study duration and to attend assessments in Cambridge.

Exclusion Criteria:

* Meet exclusion criteria for MRI scanning and/or unable to tolerate MRI environment.
* Serious co-morbid physical or psychiatric disorder which would disrupt ability to comply with study demands (e.g. a history of serious bipolar disorder; sleep apnoea not well-controlled with CPAP; insulin dependent diabetes).
* Current or past history of neurological disorders or trauma, including epilepsy, and head injury.
* Currently or recently (within 12 months) participating in a clinical trial of an investigational medicinal product (CTIMP) or another medical device.
* Lacking the capacity to consent.

Primary outcomes:
measure: The number of operationally defined outbursts
timeFrame: 15-17 months
Secondary outcomes:
measure: The Challenging Behaviour Checklist
timeFrame: 15-17 months
measure: Repetitive Behaviour Questionnaire
timeFrame: 15-17 months
measure: Life Experiences Checklist.
timeFrame: 15-17 months
measure: fMRI at resting and on-task
timeFrame: 15-17 months
measure: Participants response to challenge
timeFrame: 15-17 months
measure: Semi-structured interviews
timeFrame: 15-17 months
measure: Attention shifting ability
timeFrame: 15-17 months
measure: Salival cortisol measures
timeFrame: 15-17 months
measure: Vocal prosody
timeFrame: 15-17 months
measure: Heart Rate Variability
timeFrame: 15-17 months
Other outcomes:
Locations:
Study officials:
affiliation: University of Cambridge
name: Tony Holland, Prof.
role: PRINCIPAL_INVESTIGATOR
References: