Clinical trial NCT05417009: Autonomic Neuromodulation by Transcutaneous Nerve Stimulation in Acute Ischaemic Stroke.
Official title: Vagal Autonomic Neuromodulation by Transcutaneous Nerve Stimulation in Acute Ischaemic Stroke Requiring Mechanical Thrombectomy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Stroke
Thrombotic Stroke
Autonomic Dysfunction
Autonomic Imbalance
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
First posted: 2022-06-14
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RCT
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Blood pressure variability
timeFrame: 0-24h after mechanical thrombectomy
Secondary outcomes:
measure: Systolic and diastolic blood pressure variability in the first 24h after mechanical thrombectomy
timeFrame: 0-24h after mechanical thrombectomy
measure: Heart rate variability
timeFrame: 0-24h after mechanical thrombectomy
measure: NIH Stroke Scale (NIHSS)
timeFrame: recorded before, at 24h and 7 days after mechanical thrombectomy
measure: Organ dysfunction
timeFrame: First seven days after mechanical thrombectomy.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square
Study officials:
affiliation: William Harvey Research Institute, Queen Mary University of London
name: Gareth L Ackland, PhD FRCA
role: PRINCIPAL_INVESTIGATOR
References: