About this trial

Autonomic nervous system imbalance causes postural tachycardia and related cardiac symptoms in Postural Orthostatic Tachycardia Syndrome (POTS). The impact of POTS is more far-reaching than postural tachycardia. Several systemic, autonomic symptoms along with neuro-cognitive dysfunction leading to poor quality of life contribute to significant disability in POTS. A combination of abnormal autonomic tone, abnormal cerebral blood flow regulation, and systemic inflammation may contribute to POTS symptoms.

Auricular Vagal Neuromodulation Therapy (aVNT) has the potential for multisystem holistic benefit for patients with POTS: Autonomic neuromodulation by aVNT might address multiple aspects of POTS pathophysiology and improve POTS symptoms. It can reduce postural tachycardia by increasing the parasympathetic (PNS) and decreasing sympathetic (SNS) tone. In patients undergoing vagus nerve stimulation for various indications, an increase in PNS tone has been associated with improved middle cerebral artery velocity (MCAv) at rest and during cognitive stress. aVNT has been associated with improved cerebral blood flow and reduced infarct size in an experimental model of ischemic stroke, suggesting similar improvements in cerebral autoregulation in POTS. Vagus nerve stimulation has also been linked to improved cognitive function. The anti-inflammatory effect and improved endothelial function might improve cerebral blood flow regulation and cognitive function. The anti-inflammatory effects of aVNT may improve postural hemodynamics, reduce postural tachycardia, relieve other POTS symptoms, and improve quality of life (QoL). POTS is a complex multisystem disorder with debilitating symptoms that currently lack effective treatments. aVNT has the potential to recalibrate autonomic tone dysregulation, enhance MCAv, improve cognitive function, reduce inflammation, and ultimately improve symptoms and quality of life in POTS patients.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

POTS Patients: POTS patients will meet Canadian Cardiovascular Society criteria. 6 POTS patients will have orthostatic tachycardia >30 bpm increase in HR within 10 minutes of upright posture [>40 bpm in patients <20 years]), in the absence of orthostatic hypotension (drop in BP >20/10 mmHg), chronic symptoms of orthostatic intolerance, and no obvious cause for the tachycardia.

Age between 18-80 years

Male and female subjects are eligible

Able and willing to provide informed consent

Disqualifiers

Unable to give informed consent

Stimulant use within one week of the study

Systolic blood pressure >150 mm Hg and/or diastolic blood pressure > 100 mm Hg

Neurogenic orthostatic hypotension, prior stroke, myocardial infarction or heart failure, hematocrit < 28%

Trial design

Design model

Parallel

Treatments tested in this trial

active aVNT vs. Sham
Device
Patients in both groups will receive daily stimulation with the Parasym device, temporarily connected to the tragus of the right ear (Fig 2).54 The stimulation parameters will be frequency of 20 Hz, pulse width of 200 µs, and the stimulation amplitude will be titrated to 1 mA below the discomfort threshold, consistent with parameters used in published clinical studies.54-56 With this stimulation at just below the discomfort threshold, people will often feel the stimulation for less than 60 seconds before they lose awareness of the ongoing stimulation. The stimulation will continue for 1 hour daily for 3 months, and we will track its use with a patient diary. Participants can continue their regular activities while wearing the aVNT device, as long as it is not soaked in water. Parasym will obtain Health Canada approval for use of their device in the study.

Treatment groups

30 Participants

are divided into 2 treatment groups

Group A: active aVNTExperimental treatment 1 intervention

Group B: ShamExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Chronic aVNT in POTS induces favorable autonomic neuromodulation and decreases orthostatic tachycardia

For rigorous mechanistic evaluation and to establish causal relationships, intervention strategies (active aVNT vs. Sham) will be randomized among participants in this mechanistic study, ensuring that observed physiological effects are attributable to aVNT rather than placebo effects, baseline variability, or confounding factors. Patients with POTS will be randomly assigned to 3 months of active aVNT or sham treatment in 1:1 ratio.

Time frame

We will perform in-laboratory evaluations at baseline and 3 months post-randomization.

2

chronic aVNT in POTS induces favorable autonomic neuromodulation and decreases orthostatic tachycardia

For rigorous mechanistic evaluation and to establish causal relationships, intervention strategies (active aVNT vs. Sham) will be randomized among participants in this mechanistic study, ensuring that observed physiological effects are attributable to aVNT rather than placebo effects, baseline variability, or confounding factors. Patients with POTS will be randomly assigned to 3 months of active aVNT or sham treatment in 1:1 ratio. Patients will continue their stable ongoing non-pharmacological and pharmacological treatments for POTS.

Time frame

We will perform in-laboratory evaluations at baseline and 3 months post-randomization.

Locations

This trial has no locations.

aVNT in POTS - Pilot