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Safety and tolerability of adjunct non-invasive vagus nerve stimulation in people with parkinson's: a study protocol

Lookup NU author(s): Dr Hilmar SigurdssonORCiD, Heather Hunter, Dr Lisa AlcockORCiD, Ross Wilson, Dr Ilse Pienaar, Professor Mark BakerORCiD, Professor John-Paul TaylorORCiD, Professor Lynn RochesterORCiD, Professor Alison Yarnall



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023, The Author(s). Background: Parkinson’s disease (PD) is the fastest growing neurological condition worldwide. Recent theories suggest that symptoms of PD may arise due to spread of Lewy-body pathology where the process begins in the gut and propagate transynaptically via the vagus nerve to the central nervous system. In PD, gait impairments are common motor manifestations that are progressive and can appear early in the disease course. As therapies to mitigate gait impairments are limited, novel interventions targeting these and their consequences, i.e., reducing the risk of falls, are urgently needed. Non-invasive vagus nerve stimulation (nVNS) is a neuromodulation technique targeting the vagus nerve. We recently showed in a small pilot trial that a single dose of nVNS improved (decreased) discrete gait variability characteristics in those receiving active stimulation relative to those receiving sham stimulation. Further multi-dose, multi-session studies are needed to assess the safety and tolerability of the stimulation and if improvement in gait is sustained over time. Design: This will be an investigator-initiated, single-site, proof-of-concept, double-blind sham-controlled randomised pilot trial in 40 people with PD. Participants will be randomly assigned on a 1:1 ratio to receive either active or sham transcutaneous cervical VNS. All participants will undergo comprehensive cognitive, autonomic and gait assessments during three sessions over 24 weeks, in addition to remote monitoring of ambulatory activity and falls, and exploratory analyses of cholinergic peripheral plasma markers. The primary outcome measure is the safety and tolerability of multi-dose nVNS in PD. Secondary outcomes include improvements in gait, cognition and autonomic function that will be summarised using descriptive statistics. Discussion: This study will report on the proportion of eligible and enrolled patients, rates of eligibility and reasons for ineligibility. Adverse events will be recorded informing on the safety and device tolerability in PD. This study will additionally provide us with information for sample size calculations for future studies and evidence whether improvement in gait control is enhanced when nVNS is delivered repeatedly and sustained over time. Trial registration: This trial is prospectively registered at Registered August 23, 2021.

Publication metadata

Author(s): Sigurdsson HP, Hunter H, Alcock L, Wilson R, Pienaar I, Want E, Baker MR, Taylor J-P, Rochester L, Yarnall AJ

Publication type: Article

Publication status: Published

Journal: BMC Neurology

Year: 2023

Volume: 23

Issue: 1

Online publication date: 03/02/2023

Acceptance date: 19/01/2023

Date deposited: 17/02/2023

ISSN (electronic): 1471-2377

Publisher: BioMed Central Ltd


DOI: 10.1186/s12883-023-03081-1

PubMed id: 36737716


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