Clinical trial NCT06403475: Transcutaneous Vagus Nerve Stimulation in Aphasia After Stroke
Official title: Transcutaneous Vagus Nerve Stimulation for Language Recovery After Stroke: a Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aphasia
Chronic Stroke
Keywords: aphasia
vagus nerve stimulation
stroke
transcutaneous vagus nerve stimulation
Lead sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2024-05-07
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Aphasia is an acquired language disorder. Stroke is the most common cause of aphasia, which affects 30% of stroke survivors. Speech and Language Therapy (SLT) can help people with aphasia but it may not be provided at the required intensity. Access to therapy is often limited after the first few months following stroke. People with aphasia can improve with therapy many years after stroke but these benefits have not been found to translate to day to day conversation.

Transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive technique which involves stimulating a branch of the vagus nerve through the skin of the ear, using a small earpiece. This technique is safe and has been approved for use in headache. There is promising evidence that tVNS can improve motor rehabilitation in chronic stroke. This technique may be helpful in aiding language recovery in individuals with chronic aphasia.

The current pilot study will primarily assess the feasibility, safety and tolerability of self-directed tVNS paired with computer-based SLT, in individuals with chronic stroke-related aphasia. Secondly, the study aims to explore the effect of the intervention on word-finding ability and to explore potential mechanisms of action. Participants will be randomly allocated to an active or sham tVNS group. Participants will be asked to use the stimulation device at home for 6 weeks, whilst completing computer-based SLT. To date, there are no published studies exploring the use of tVNS in aphasia. An indication of study feasibility may support the development of a larger RCT to explore treatment efficacy.

Detailed description: Aphasia is an acquired communication disorder, characterised by difficulties with the production and/or understanding of language. Stroke is the most common cause of aphasia which affects approximately 30% of stroke survivors. Many individuals are left with chronic deficits. Speech and Language Therapy (SLT) is the gold-standard treatment for aphasia but access to therapy is limited beyond the first few months of recovery. Individuals with chronic aphasia (\>6 months) can benefit from SLT input. Computer-based SLT can lead to improvements in word-finding for people with aphasia, many years after stroke (Palmer et al., 2019). Improvements have not been found to translate to day-to-day conversation.

Vagus Nerve Stimulation (VNS) paired with upper limb rehabilitation has proved beneficial in chronic stroke. Transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive technique which involves stimulating a branch of the vagus nerve through the skin of the ear, using a small earpiece. This technique is safe and has been approved for use in headache. The use of tVNS in chronic stroke is currently being explored, with promising findings when paired with upper limb rehabilitation exercises. To date, there are no published studies exploring the use of tVNS in chronic aphasia. Pairing tVNS with an SLT intervention may have the potential to promote language recovery in chronic stroke. An indication of study feasibility may support the development of a larger RCT to explore treatment efficacy.

This is a single centre, single blind, pilot randomised controlled trial. The primary aim is to explore the safety, tolerability and feasibility of self-directed computer-based SLT combined with tVNS, in individuals with chronic-stroke related aphasia. Secondary aims include exploring any indication of effect of the intervention on word-finding ability (trained words, generalisability to untrained words and conversation). Additionally, the study aims to explore potential mechanisms of action.

Participants will be asked to use the stimulation device alongside computer-based SLT, at home for 6 weeks. SLT training will include naming pictures of 30 personally relevant words, selected by the participant prior to the commencement of the intervention and uploaded onto the software. The SLT software (Step by Step) uses a self-guided errorless learning approach and will be completed on an ipad. The researcher will check-in with the participant each week to monitor any concerns, side effects and monitor engagement with the programme.

Potential participants will be recruited from Sheffield, using the NHS PHIND database. Accessible study invitations will be sent to potential participants. The Consent Support Tool will be used to ascertain the most appropriate way to provide study information. All participants will have capacity to consent to the study. Participants will be randomly allocated (SealedEnvelope Ltd) to an active or sham tVNS group, stratified according to language score. Participants will be blinded to group allocation.

The tVNS device will be applied to the ear (tragus or earlobe), depending on group allocation. The tVNS device (Nurosym/ Parasym II) is a UKCE marked device, indicated for off-label use in the current study. tVNS use is safe however it has been associated with mild and transitory side effects such as pain or irritation at the stimulation site, headache and nasopharyngitis (Redgrave et al 2018). Stimulation parameters are in line with previous studies:

* Pulse Width: 250µs
* Frequency: 25Hz
* Intensity: individual tolerability (below pain threshold)
* Duration: 45 minutes daily for 6 weeks

Language assessments will be taken at baseline, end of treatment (6 weeks) and at follow-up (12 weeks). To explore potential mechanisms, blood samples, heart rate variability (HRV) and pupillometry measures will be taken at baseline and end of treatment. The Functional near infrared spectroscopy (fNIRS; LUMO, Gowerlabs) will be used on a subset of participants to explore cortical activation in the frontal lobes in response to tVNS at baseline and end of treatment (6 weeks). Outcome measures will be undertaken by a trained member of the research team.

Eligibility criteria: Inclusion Criteria:

* Supratentorial stroke at least 6 months prior to recruitment
* Aphasia (with word finding difficulties)
* Ability to engage in the programme (support can be provided for cognitive or receptive difficulties)
* Sufficient vision to engage in the computer-based SLT programme

Exclusion Criteria:

* Implanted devices (e.g. pacemaker) or implanted stimulation devices
* Currently receiving a programme of Speech and Language Therapy (SLT)
* Damage to the vagus nerve
* Symptomatic bradycardia/ 2nd or 3rd heart block
* Pregnancy
* Unable to speak English
* Severe deafness (despite using hear aids)

Primary outcomes:
measure: Safety: The number of adverse events reported that are associated with tVNS
timeFrame: 6 weeks
measure: Tolerability: The number and intensity of symptoms reported
timeFrame: 6 weeks
measure: Percentage of participants completing the study intervention and outcome measures
timeFrame: 24 months
Secondary outcomes:
measure: Picture Naming (personally relevant)
timeFrame: Week 0; Week 6; Week 12
measure: The Comprehensive Aphasia Test (CAT): Naming Objects
timeFrame: Week 0; Week 6; Week 12
measure: Conversation: The number of trained words used in conversation
timeFrame: Week 0; Week 6; Week 12
measure: Brain Derived Neurotrophic Factor (BDNF) (ng/ml)
timeFrame: Week 0; Week 6
measure: Inflammatory markers (pg/ml)
timeFrame: Week 0; Week 6
measure: Heart Rate Variability (HRV)
timeFrame: Week 0; Week 6
measure: Pupillary Reactivity
timeFrame: Week 0; Week 6
Other outcomes:
Locations:
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
name: Dr Ali Ali
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sheffield
name: Prof. Arshad Majid
role: STUDY_DIRECTOR
affiliation: University of Sheffield
name: Prof. Rebecca Palmer
role: STUDY_DIRECTOR
References:
citation: Palmer R, Dimairo M, Cooper C, Enderby P, Brady M, Bowen A, Latimer N, Julious S, Cross E, Alshreef A, Harrison M, Bradley E, Witts H, Chater T. Self-managed, computerised speech and language therapy for patients with chronic aphasia post-stroke compared with usual care or attention control (Big CACTUS): a multicentre, single-blinded, randomised controlled trial. Lancet Neurol. 2019 Sep;18(9):821-833. doi: 10.1016/S1474-4422(19)30192-9.
citation: Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018 Nov-Dec;11(6):1225-1238. doi: 10.1016/j.brs.2018.08.010. Epub 2018 Aug 23.