Autonomic Neuromodulation by Transcutaneous Nerve Stimulation in Acute Ischaemic Stroke.

NCT ID: NCT05417009

Last Updated: 2025-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-26
• Study Completion Date: 2023-07-21

Brief Summary

Autonomic modulation by transcutaneous vagal nerve stimulation in acute ischaemic stroke requiring mechanical thrombectomy: a phase IIa, sham controlled randomised trial.

Detailed Description

Loss of autonomic variability is strongly associated with adverse outcomes after ischaemic stroke. Removing blood clots from the brain by mechanical thrombectomy has revolutionised the management of stroke, but more than 50% of patients do not regain functional independence.(PMID:26898852) Blood pressure (BP) control is important, since low and high BP (BP variability) are strongly associated with poor patient outcomes after thrombectomy. (PMIDs:32961389;31964286) Autonomic dysfunction causes labile blood pressure. Intact autonomic function is required to control blood pressure and potentially improve recovery after stroke. Impairment of baroreflex autonomic function, due to reduced vagal activity is associated with extreme BP variability, leading to further brain injury and cardiovascular complications.(PMID:30371208) Reduced baroreflex control is related to poor patient outcomes after stroke, independent of absolute blood pressure.(PMID:19834010) Reversing baroreflex and vagal dysfunction is, therefore, widely held to have the potential to improve cardiovascular control and patient outcome in this context.(PMID:19834010)

Non-invasive peripheral neuromodulation restores autonomic control. Vagal nerve stimulation improves autonomic control and reverses baroreflex dysfunction (PMIDs:28949064) but this has previously required surgically implanted devices which are expensive and impractical in the context of acute stroke. Afferent Electronic have achieved the same effect as these implantable devices by non-invasive transcutaneous autonomic neuromodulation (TAN). We have used this simple, safe, hand-held, low-cost device to increase vagal activity and baroreflex sensitivity through non-invasive, painless stimulation of nerves located in the outer ear to control blood pressure.

Baroreflex sensitivity can be increased at the bedside by TAN for 30 minutes following acute trauma. If this can be replicated in thrombectomy patients, it will aid recovery and rehabilitation through five complementary mechanisms where it has been clinically demonstrated that increasing vagal nerve activity:

1. Restore baroreflex sensitivity;

2. Increase blood flow to ischaemic brain tissue through vagal activation.(PMID:27357059)

3. Dampen cerebral/systemic inflammation.(PMID:26723020);

4. Reduce atrial fibrillation and myocardial injury,(PMIDs:5744003,22739118) which are common after stroke, and independently predict cognitive decline and cardiovascular mortality

5. Allows immediate commencement of vagal nerve stimulation, which has recently been shown to enhance upper-limb rehabilitation.(PMID:33894832) Our proof-of-concept data shows daily TAN reduces BP and BP variability lasting several months even in drug-resistant hypertensive patients. In this proof-of-concept randomised sham-controlled trial, we will examine whether early TAN on presentation for mechanical thrombectomy improves autonomic function in patients with acute ischaemic stroke by reducing blood pressure lability.

Conditions

Ischemic Stroke; Thrombotic Stroke; Autonomic Dysfunction; Autonomic Imbalance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Stimulation

Electrodes attached bliaterally to tragus nerve region of outer ear, with appropriate device settings to deliver current.

Group Type: ACTIVE_COMPARATOR

trans-cutaneous auricular sensory stimulation

Intervention Type: DEVICE

Transcutaneous auricular sensory stimulation

Electrode attachment only.

Electrodes attached bliaterally to tragus nerve region of outer ear, with device switched off \[blinded to operator\].

Group Type: SHAM_COMPARATOR

trans-cutaneous auricular sensory stimulation

Intervention Type: DEVICE

Transcutaneous auricular sensory stimulation

Interventions

trans-cutaneous auricular sensory stimulation

Transcutaneous auricular sensory stimulation

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Undergoing mechanical thrombectomy for acute ischaemic stroke requiring general or sedation.
• Established hypertensive and/or hypertensive on admission for mechanical thrombectomy [systolic BP >140mmHg; diastolic BP >80mmHg]

Exclusion Criteria

• Current participation in a clinical trial of a treatment with a similar biological mechanism.
• Previous enrolment into VANS trial.
• Anatomical or other contraindication to trans-cutaneous auricular sensory stimulation
• Pregnancy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Queen Mary University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gareth L Ackland, PhD FRCA

Role: PRINCIPAL_INVESTIGATOR

William Harvey Research Institute, Queen Mary University of London

Locations

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square

London, , United Kingdom

Countries

United Kingdom

References

Ackland GL, Martin T, Joseph M, Dias P, Hameed R, Gutierrez Del Arroyo A, Hewson R, Abbott TEF, Spooner O, Bhogal P. Transauricular nerve stimulation in acute ischaemic stroke requiring mechanical thrombectomy: Protocol for a phase 2A, proof-of-concept, sham-controlled randomised trial. PLoS One. 2023 Dec 22;18(12):e0289719. doi: 10.1371/journal.pone.0289719. eCollection 2023.

Reference Type: DERIVED

PMID: 38134136 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

314067

Identifier Type: -

Identifier Source: org_study_id