Transcutaneous Vagal Nerve Stimulation (tVNS)NCT03689621
Proof of Concept Study of Vagus Nerve Stimulation
A study testing Transcutaneous vagus nerve stimulation (tVNS) in people with Transcutaneous Vagal Nerve Stimulation (tVNS) and Prader-Willi Syndrome, run by Jessica Beresford-Webb.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transcutaneous Vagal Nerve Stimulation (tVNS), Prader-Willi Syndrome
- What is being tested?
- Transcutaneous vagus nerve stimulation (tVNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2016to 31 Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
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
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.
- Being tested
- Transcutaneous vagus nerve stimulation (tVNS)
- Medical subject headings
- Prader-Willi Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous vagus nerve stimulation (tVNS)Device
| Study group | Role | What they receive |
|---|---|---|
| Transcutaneous vagal nerve stimulation (tVNS) | Active comparator | tVNS administered for 4 hours each day and behaviour is recorded. Receives: Device: Transcutaneous vagus nerve stimulation (tVNS) |
| Baseline | Placebo comparator | tVNS worn but not switched on whilst collecting behavioural data. Receives: Device: Transcutaneous vagus nerve stimulation (tVNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of operationally defined outbursts
Measured using participant and informant diaries.
Measured: 15-17 months
Secondary outcomes (10)
The Challenging Behaviour Checklist
Scores on rating scale, repeated over time. Score range 50-55. higher score indicates more severe behaviour.
Measured: 15-17 months
Repetitive Behaviour Questionnaire
Scores on rating scale, repeated over time. Total scores range between 20-60. The higher toe score the worse behaviours are.
Measured: 15-17 months
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.
Measured: 15-17 months
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
Measured: 15-17 months
Participants response to challenge
Using methodology developed by Prof Oliver, filmed and subsequently rated blind for emotional and behavioural changes.
Measured: 15-17 months
Semi-structured interviews
With participants and carers to probe about any observed subtle changes in behaviour. Analysed thematically.
Measured: 15-17 months
Attention shifting ability
Tested via go-no-go task developed for people with PWS by Woodcock et al (2009). Reaction times analysed.
Measured: 15-17 months
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).
Measured: 15-17 months
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.
Measured: 15-17 months
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.
Measured: 15-17 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2018
- Study start1 Jan 2016
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transcutaneous Vagal Nerve Stimulation (tVNS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jessica Beresford-Webb
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Prader-Willi Research
- Responsible party
- Sponsor-investigator, Jessica Beresford-Webb, University of Cambridge
- Investigators
- Tony Holland, Prof., Principal investigator, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03689621
- Sponsor's protocol ID
- 15/EE/0450
- Status last verified
- Apr 2019
- First submitted
- 26 Sep 2018
- Last updated
- 17 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03689621
- Acronym / sponsor ID
- 15/EE/0450
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Jessica Beresford-WebbUniversity, hospital or other
- Collaborators
- Foundation for Prader-Willi Research
- Study start
- 1 Jan 2016 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 28 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transcutaneous vagal nerve stimulation (tVNS) | Active comparator | Device: Transcutaneous vagus nerve stimulation (tVNS)tVNS administered for 4 hours each day and behaviour is recorded. |
| Baseline | Placebo comparator | Device: Transcutaneous vagus nerve stimulation (tVNS)tVNS worn but not switched on whilst collecting behavioural data. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous vagus nerve stimulation (tVNS) | Device | Baseline, Transcutaneous vagal nerve stimulation (tVNS) |
Primary outcome
The number of operationally defined outbursts
Time frame: 15-17 months
Measured using participant and informant diaries.
10 secondary outcomes
The Challenging Behaviour Checklist
Time frame: 15-17 months
Repetitive Behaviour Questionnaire
Time frame: 15-17 months
Life Experiences Checklist.
Time frame: 15-17 months
fMRI at resting and on-task
Time frame: 15-17 months
Participants response to challenge
Time frame: 15-17 months
Semi-structured interviews
Time frame: 15-17 months
Attention shifting ability
Time frame: 15-17 months
Salival cortisol measures
Time frame: 15-17 months
Vocal prosody
Time frame: 15-17 months
Heart Rate Variability
Time frame: 15-17 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tony Holland, Prof. principal investigator
University of Cambridge
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous vagus nerve stimulation (tVNS) in people with Transcutaneous Vagal Nerve Stimulation (tVNS) and Prader-Willi Syndrome, run by Jessica Beresford-Webb.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of operationally defined outbursts (time frame: 15-17 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2019.