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Completed

NCT Number: NCT03689621

Proof of Concept Study of Vagus Nerve Stimulation

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.

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Key information

Conditions

Transcutaneous Vagal Nerve Stimulation (tVNS) Abnormalities, Multiple Chromosome Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Imprinting Disorders Intellectual Disability Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Prader-Willi Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Transcutaneous Vagus Nerve Stimulation (tVNS)

Device

Primary outcomes

  1. The number of operationally defined outbursts

    Time frame: 15-17 months

    Measured using participant and informant diaries.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Semi-structured interviews

    Time frame: 15-17 months

    With participants and carers to probe about any observed subtle changes in behaviour. Analysed thematically.

  7. 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.

  8. 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).

  9. 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.

  10. 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.

Sponsors and collaborators

Lead sponsor

Jessica Beresford-Webb

Other

Collaborators

  • Foundation for Prader-Willi Research

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Sep 28, 2018
Registry last updated
Apr 17, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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