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
About this trial
This is an interventional treatment trial for Transcutaneous Vagal Nerve Stimulation (tVNS)
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.
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
NCT ID
NCT03689621
First Posted
September 26, 2018
Last Updated
April 16, 2019
Sponsor
Jessica Beresford-Webb
Collaborators
Foundation for Prader-Willi Research
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
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Proof of Concept Study of Vagus Nerve Stimulation
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