NCT06374693

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for not_applicable

Timeline
3mo left

Started Apr 2024

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress90%
Apr 2024Jul 2026

First Submitted

Initial submission to the registry

March 25, 2024

Completed
23 days until next milestone

Study Start

First participant enrolled

April 17, 2024

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 19, 2024

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2026

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2026

Last Updated

March 20, 2026

Status Verified

February 1, 2026

Enrollment Period

2.1 years

First QC Date

March 25, 2024

Last Update Submit

March 17, 2026

Conditions

Keywords

subarachnoid haemorrhagevagus nerve stimulationtranscutaneous vagus nerve stimulationaneurysmal subarachnoid haemorrhage

Outcome Measures

Primary Outcomes (2)

  • Monitor tolerability for tVNS

    Symptom severity scores of mild or moderate in less than 1/3 of participants able to report symptoms

    4 weeks

  • Assess study feasibility

    recruit \>1 patient per month of recruitment, and \>80% of recruited patients completing primary outcome measures

    24 months

Secondary Outcomes (12)

  • Monitor safety criteria for tVNS

    4 weeks

  • Rates of delayed cerebral ischaemia (DCI)

    4 weeks

  • Inpatient mortality

    4 weeks

  • Length of inpatient stay

    From the date of admission to the date of discharge from hospital up to 100 months

  • Rates of inpatient complications

    From the date of admission to the date of discharge from hospital up to 100 months

  • +7 more secondary outcomes

Study Arms (2)

Stimulation

EXPERIMENTAL

The intervention will take place for 45 minutes twice a day for 5 days after securing the aneurysm

Device: Transcutaneous Vagus Nerve Stimulation

Sham

SHAM COMPARATOR

The placebo group will receive the same intervention, but the device will be in 'sham' mode (i.e. attached to the earlobe).

Device: Sham Transcutaneous Vagus Nerve Stimulation

Interventions

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.

Sham

* 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.

Stimulation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \>18
  • Admitted to STH (Sheffield Teaching Hospital) neurosurgery department
  • Confirmed aneurysmal SAH on vascular imaging
  • Within 5 days of 'Securing' aneurysm (i.e., successfully coiled or surgically following rupture)

You may not qualify if:

  • Current or prior use of a vagus nerve stimulation
  • Symptomatic bradycardia or PPM insertion
  • Complete heart block
  • Implantation of any other electrical stimulator (e.g. DBS)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Sheffield

Sheffield, South Yorkshire, S10 2HQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Dr Ali Ali

    Sheffield Teaching Hospitals NHS Foundation Trust

    PRINCIPAL INVESTIGATOR
  • Professor Arshad Majid

    University of Sheffield

    STUDY DIRECTOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 25, 2024

First Posted

April 19, 2024

Study Start

April 17, 2024

Primary Completion (Estimated)

May 30, 2026

Study Completion (Estimated)

July 31, 2026

Last Updated

March 20, 2026

Record last verified: 2026-02

Locations