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Proof of Concept Study of Vagus Nerve Stimulation

Primary Purpose

Transcutaneous Vagal Nerve Stimulation (tVNS), Prader-Willi Syndrome

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Transcutaneous vagus nerve stimulation (tVNS)
Sponsored by
Jessica Beresford-Webb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transcutaneous Vagal Nerve Stimulation (tVNS)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Transcutaneous vagal nerve stimulation (tVNS)

    Baseline

    Arm Description

    tVNS administered for 4 hours each day and behaviour is recorded.

    tVNS worn but not switched on whilst collecting behavioural data.

    Outcomes

    Primary Outcome Measures

    The number of operationally defined outbursts
    Measured using participant and informant diaries.

    Secondary Outcome Measures

    The Challenging Behaviour Checklist
    Scores on rating scale, repeated over time. Score range 50-55. higher score indicates more severe behaviour.
    Repetitive Behaviour Questionnaire
    Scores on rating scale, repeated over time. Total scores range between 20-60. The higher toe score the worse behaviours are.
    Life Experiences Checklist.
    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
    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
    Using methodology developed by Prof Oliver, filmed and subsequently rated blind for emotional and behavioural changes.
    Semi-structured interviews
    With participants and carers to probe about any observed subtle changes in behaviour. Analysed thematically.
    Attention shifting ability
    Tested via go-no-go task developed for people with PWS by Woodcock et al (2009). Reaction times analysed.
    Salival cortisol measures
    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
    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
    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.

    Full Information

    First Posted
    September 26, 2018
    Last Updated
    April 16, 2019
    Sponsor
    Jessica Beresford-Webb
    Collaborators
    Foundation for Prader-Willi Research
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03689621
    Brief Title
    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

    2. Study Status

    Record Verification Date
    April 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    January 1, 2016 (Actual)
    Primary Completion Date
    December 31, 2018 (Actual)
    Study Completion Date
    December 31, 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Jessica Beresford-Webb
    Collaborators
    Foundation for Prader-Willi Research

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Transcutaneous Vagal Nerve Stimulation (tVNS), Prader-Willi Syndrome

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Crossover Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    9 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Transcutaneous vagal nerve stimulation (tVNS)
    Arm Type
    Active Comparator
    Arm Description
    tVNS administered for 4 hours each day and behaviour is recorded.
    Arm Title
    Baseline
    Arm Type
    Placebo Comparator
    Arm Description
    tVNS worn but not switched on whilst collecting behavioural data.
    Intervention Type
    Device
    Intervention Name(s)
    Transcutaneous vagus nerve stimulation (tVNS)
    Primary Outcome Measure Information:
    Title
    The number of operationally defined outbursts
    Description
    Measured using participant and informant diaries.
    Time Frame
    15-17 months
    Secondary Outcome Measure Information:
    Title
    The Challenging Behaviour Checklist
    Description
    Scores on rating scale, repeated over time. Score range 50-55. higher score indicates more severe behaviour.
    Time Frame
    15-17 months
    Title
    Repetitive Behaviour Questionnaire
    Description
    Scores on rating scale, repeated over time. Total scores range between 20-60. The higher toe score the worse behaviours are.
    Time Frame
    15-17 months
    Title
    Life Experiences Checklist.
    Description
    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.
    Time Frame
    15-17 months
    Title
    fMRI at resting and on-task
    Description
    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
    Time Frame
    15-17 months
    Title
    Participants response to challenge
    Description
    Using methodology developed by Prof Oliver, filmed and subsequently rated blind for emotional and behavioural changes.
    Time Frame
    15-17 months
    Title
    Semi-structured interviews
    Description
    With participants and carers to probe about any observed subtle changes in behaviour. Analysed thematically.
    Time Frame
    15-17 months
    Title
    Attention shifting ability
    Description
    Tested via go-no-go task developed for people with PWS by Woodcock et al (2009). Reaction times analysed.
    Time Frame
    15-17 months
    Title
    Salival cortisol measures
    Description
    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).
    Time Frame
    15-17 months
    Title
    Vocal prosody
    Description
    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.
    Time Frame
    15-17 months
    Title
    Heart Rate Variability
    Description
    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.
    Time Frame
    15-17 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Tony Holland, Prof.
    Organizational Affiliation
    University of Cambridge
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Proof of Concept Study of Vagus Nerve Stimulation

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