Autonomic Neuromodulation by Transcutaneous Nerve Stimulation in Acute Ischaemic Stroke.

Ischemic Stroke Clinical Trial

— VANS  

Official title:

Vagal Autonomic Neuromodulation by Transcutaneous Nerve Stimulation in Acute Ischaemic Stroke Requiring Mechanical Thrombectomy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05417009
• Other study ID #: 314067
• Status: Completed
• Phase: N/A
• Start date: April 26, 2023
• Est. completion date: July 21, 2023

Study information

• Verified date: August 2023
• Source: Queen Mary University of London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 21, 2023
• Est. primary completion date: July 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autonomic Dysfunction
• Autonomic Imbalance
• Autonomic Nervous System Diseases
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Primary Dysautonomias
• Stroke
• Thrombotic Stroke

Intervention

Device:
• trans-cutaneous auricular sensory stimulation
Transcutaneous auricular sensory stimulation

Locations

Country	Name	City	State
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Queen Mary University of London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood pressure variability	Coefficient of variation of systolic blood pressure	0-24h after mechanical thrombectomy
Secondary	Systolic and diastolic blood pressure variability in the first 24h after mechanical thrombectomy	Systolic and diastolic blood pressure standard deviation, average real variability, successive variation and residual standard deviation	0-24h after mechanical thrombectomy
Secondary	Heart rate variability	Time and frequency domain measures of autonomic cardiac modulation	0-24h after mechanical thrombectomy
Secondary	NIH Stroke Scale (NIHSS)	FDA-approved primary outcome measure for stroke in early phase II trials.	recorded before, at 24h and 7 days after mechanical thrombectomy
Secondary	Organ dysfunction	Clinical need for intravenous pharmacological support for blood pressure [pressors or intravenous antihypertensive medication]; arrythmias; myocardial injury [high sensitivity troponin]; hospital-acquired infection.	First seven days after mechanical thrombectomy.