aVNT in POTS - Pilot

NCT07026643 | Not Yet Recruiting

• 1 other identifier: REB25-1014
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Postural Orthostatic Tachycardia Syndrome (POTS)

Keywords

Postural Orthostatic Tachycardia Syndrome; Auricular vagal neuromodulation therapy

Outcome Measures

Primary Outcomes (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.

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

• 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.

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

Study Arms (2)

active aVNT

EXPERIMENTAL

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. We will perform in-laboratory evaluations at baseline and 3 months post-randomization. We will also collect data on HR and orthostatic tachycardia at home in between the laboratory evaluations, using a wearable monitor.

Device: active aVNT vs. Sham

Sham

EXPERIMENTAL

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. We will perform in-laboratory evaluations at baseline and 3 months post-randomization. We will also collect data on HR and orthostatic tachycardia at home in between the laboratory evaluations, using a wearable monitor.

Device: active aVNT vs. Sham

Interventions

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.

Sham; active aVNT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%
• Significant comorbidities (cardiovascular, metabolic, renal, respiratory, cancer, immunological or hematological)
• History of vagotomy, permanent pacemakers
• Pregnant or nursing females.

Sponsors & Collaborators

• University of Calgary: lead

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Study Officials

• Satish Raj, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiyao Qi, MD

CONTACT

14032107627; jiyao.qi@ucalgary.ca

Rasha Hamzeh, RN, MSN

CONTACT

4032208897; rasha.hamzeh1@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization will be performed on the day of the baseline evaluation before giving the participant their aVNT device. To minimize concealment bias, variable block randomization (blocks of 4 or 6) will be used. The site will access the central RedCap randomization module to determine the assignment from the randomization tables. An unblinded coordinator at the site will perform the randomization and deliver the aVNT (with appropriate programming) to each participant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients in both groups will receive daily stimulation with the Parasym device, temporarily connected to the tragus of the right ear. 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.

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 18, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: May 1, 2026

Record last verified: 2026-04