Autonomic Neuromodulation by Transcutaneous Nerve Stimulation in Acute Ischaemic Stroke.
Condition: Ischemic Stroke; Thrombotic Stroke; Autonomic Dysfunction; Autonomic Imbalance
MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Autonomic Nervous System Diseases; Primary Dysautonomias; Thrombotic Stroke; Ischemia
Study type: Interventional

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.
    

Intervention name(s): trans-cutaneous auricular sensory stimulation
Intervention type(s): Device
Intervention description(s): Transcutaneous auricular sensory stimulation
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: RCT
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment