Investigating the Tolerability and Feasibility of tVNS Following aSAH

Summary

After a subarachnoid haemorrhage, complications are common and increase the overall rate of disability and death from the condition. Despite some advances in preventing, detecting and treating these complications, the rates of complications and associated risks remain high. Further research into ways to reduce complications of subarachnoid haemorrhage.

Transcutaneous vagus nerve stimulation (tVNS) is a technique where a small handheld device is attached to an earpiece which stimulates the nerves to the ear. This is given for short periods and may help improve blood flow and reduce inflammation in the brain. The intervention has been safely used and licensed in seizures, headache and severe depression.

This study will look to see if it is feasible and tolerable to have tVNS twice daily for 5 days after subarachnoid haemorrhage, and whether it can help reduce the risk of complications from subarachnoid haemorrhage.

The participant will be randomly allocated to receive either tVNS or a dummy intervention, known as sham.

The researchers will collect some personal and clinical details such as diagnosis, medications, age, blood test results, as well as some details about the subarachnoid haemorrhage.

The researchers will also complete brief questionnaires with the participant to assess symptoms. They will take measurements of heart rate, pupil response, and brain activity using a cap. The participant will then be randomly allocated to either receive the tVNS or sham intervention.

Next, the research team will apply the earpiece to their ear twice a day for 45 minutes, for a total of 5 days.

At the end of the 5-day study period, the intervention will be complete. The researchers will arrange a follow-up meeting on discharge and at 6 weeks, to assess the participants symptoms and recovery.

Previous studies have shown that tVNS is safe and well tolerated, including a recent review of tVNS studies which evaluated the side effects experienced by 1322 patients receiving tVNS.

The main side effects include localised tingling/numbness/pain/redness around the ear (17%), headaches (3%), dizziness (1%), facial droop (1%), nausea (1%), nasal discharge (2%). Rarely, palpitations or a slow heart rate may occur.

They will continue to receive full medical treatment and observation alongside the study. They are free to withdraw from this study if they find it too demanding on top of their other activities.

Conditions

• Subarachnoid Haemorrhage From Cerebral Aneurism Rupture

Interventions

DEVICE

Transcutaneous Vagus Nerve Stimulation

* Pulse width - 25ms * Frequency - device default (20 or 25Hz) * Intensity - below pain threshold. * Frequency - 45 minutes twice daily. On the basis of similarity to other studies, practicalities on the ward and clinical scenario We have chosen a duration of 5 days based on the usual clinical pathway of inpatient management at the Royal Hallamshire Hospital, and have chosen to deliver the treatment twice daily to optimise the dose. This is a pilot study with feasibility outcomes and as such we will be exploring the feasibility of this treatment regimen. The Parasym Device will be applied to the left tragus (figure 1) as this is the most common site for tVNS delivery in neurological studies and is associated with few afferents to the heart.

DEVICE

Sham Transcutaneous Vagus Nerve Stimulation

The active intervention will be compared to sham tVNS where the vagal nerve stimulator will be attached to the earlobe instead of the tragus, in keeping with evidence that this does not cause vagus nerve stimulation and is in line with sham methods used in other studies. We do not anticipate that patients will have the intervention long enough to become familiar with the common sensations associated with true tVNS intervention. At the end of the intervention period, participants will be asked if they thought they had received true of sham tVNS to understand the blinding ability of the sham.

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust

  lead OTHER

Principal Investigators

• Dr Ali Ali · Sheffield Teaching Hospitals NHS Foundation Trust

• Professor Arshad Majid · University of Sheffield

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-04-17

Primary Completion

2026-05-30

Completion

2026-07-31

Countries

• United Kingdom

Study Locations