Proof of Concept Study of Vagus Nerve Stimulation

NCT03689621 | Completed

• 1 other identifier: 15/EE/0450
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• The number of operationally defined outbursts

  Measured using participant and informant diaries.

  15-17 months

Secondary Outcomes (10)

• The Challenging Behaviour Checklist

  15-17 months

• Repetitive Behaviour Questionnaire

  15-17 months

• Life Experiences Checklist.

  15-17 months

• fMRI at resting and on-task

  15-17 months

• Participants response to challenge

  15-17 months

Study Arms (2)

Transcutaneous vagal nerve stimulation (tVNS)

ACTIVE COMPARATOR

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

Device: Transcutaneous vagus nerve stimulation (tVNS)

Baseline

PLACEBO COMPARATOR

tVNS worn but not switched on whilst collecting behavioural data.

Device: Transcutaneous vagus nerve stimulation (tVNS)

Interventions

Transcutaneous vagus nerve stimulation (tVNS) DEVICE

Baseline; Transcutaneous vagal nerve stimulation (tVNS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jessica Beresford-Webb: lead
• Foundation for Prader-Willi Research: collaborator

MeSH Terms

Conditions

Prader-Willi Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Tony Holland, Prof.

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Assistant

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: September 28, 2018
• Study Start: January 1, 2016
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: April 17, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share