Tragus Stimulation for POTS Treatment

NCT07163130 | Not Yet Recruiting

• 1 other identifier: TREATPOTS3RDCARDIO
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Postural Tachycardia Syndrome (POTS) is a form of dysautonomia characterized by an abnormal cardiovascular response to orthostatic challenges. Individuals afflicted with POTS typically exhibit a heart rate increase of more than 30 beats per minute (bpm) within 10 minutes of assuming an upright posture from a supine or sitting position. This abnormal response is often accompanied by symptoms, such as orthostatic intolerance, dizziness, weakness, fatigue, and, in certain instances, syncope. Lately, there is revived interest in POTS, as it has been quite frequently reported as a manifestation of autonomic dysfunction among patients with long COVID. POTS primarily affects the younger demographic, particularly women, and its pathophysiology appears to be multifactorial, involving autonomic neuropathy, hyperadrenergic state, and inadequate blood volume regulation. Diagnostic criteria commonly include a sustained heart rate increase without significant orthostatic hypotension. The pathophysiological mechanisms of POTS are complex and not fully elucidated. Management strategies encompass lifestyle modifications, exercise programs, and pharmacotherapy, but their efficacy is modest. Transcutaneous auricular vagus nerve stimulation (tVNS) is an emerging therapeutic modality in cardiovascular diseases. tVNS has been shown to exert antiadrenergic and anti-inflammatory effects in humans. Recently, tVNS has been tested in experimental and human POTS, leading to improved autonomic function, reduction of anti-autonomic autoantibodies and inflammatory cytokines. However, the exact patient characteristics that would identify a patient likely to respond to tVNS as well as further mechanistic and clinical endpoints with tVNS have not been explored. The aim of this study is to assess and characterize in detail the effect of tVNS in patients with POTS. This is a prospective crossover study in patients with POTS. The expected study duration is approximately 15 months from the time the first subject is enrolled to study termination. Patient enrollment is planned to take place at 3-4 major centers in Greece.

Conditions

Postural Orthostatic Tachycardia Syndrome (POTS)

Outcome Measures

Primary Outcomes (1)

• Difference in Heart Rate change during the posture test, between the 2 treatment periods (on-treatment versus off-treatment).

  Difference in Heart Rate change during the posture test, between the 2 treatment periods (active versus sham). The Heart rate change will be calculated as Standing Heart rate minus Supine Heart rate, the former being defined as the maximal heart rate recorded during a 10-minute period from erection from the supine to the standing position and the latter as the heart rate immediately before standing (the patient will remain at the supine position in a quiet room for at least 5 minutes before rising to the standing position).

  Through study completion, up to 16 months from study start date

Secondary Outcomes (1)

• Autonomic symptoms assessed using the Malmo POTS Score questionnaire

  Through study completion, up to 16 months from study start date

Study Arms (2)

Treatment sequence: Active - Sham

OTHER

This arm will undergo active treatment first and then (after a wash-out period) sham treatment.

Device: Transcutaneous auricular vagus nerve stimulation

Treatment sequence: Sham - Active

OTHER

This arm will undergo sham treatment first and then (after a wash-out period) active treatment

Device: Transcutaneous auricular vagus nerve stimulation

Interventions

Transcutaneous auricular vagus nerve stimulation DEVICE

Transcutaneous auricular vagus nerve stimulation (tVNS) is an emerging therapeutic modality in cardiovascular diseases. tVNS has been shown to exert antiadrenergic and anti-inflammatory effects in humans. Recently, tVNS has been tested in experimental and human POTS, leading to improved autonomic function, reduction of anti-autonomic autoantibodies and inflammatory cytokines. Parasym device; Parasym Health, London, United Kingdom Frequency: 20Hz, pulse width: 200μs, amplitude will be individually titrated to 1 mA below the level that caused mild discomfort.

Treatment sequence: Active - Sham; Treatment sequence: Sham - Active

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥18 years
• Diagnosis of POTS, defined as heart rate increase \>30 beats/min from supine within 10 minute of standing, in the absence of orthostatic hypotension (\>20/10 mm Hg fall in blood pressure), with chronic symptoms (\>6 months), and in the absence of other acute causes of orthostatic tachycardia,
• Signed written informed consent by the patient for participation in the study and agreement to comply with the study procedures and the follow-up schedule.

You may not qualify if:

• Hypertension (\>150 mmHg systolic and \>100 mmHg diastolic) based on history or findings at screening.
• Orthostatic hypotension (consistent drop in blood pressure \>20/10 mmHg with 10 min of standing)
• History or presence of significant neurological, immunological, or hematological disorders
• Cardiovascular disease, such as myocardial infarction within 6 months
• Patients on renal dialysis.
• Life expectancy of \<12 months
• Currently pregnant women or women planning on becoming pregnant ≤ 5 months
• Patients with active implants (such as a cardiac pacemaker, implantable cardioverter-defibrillator, or a cochlear implant)
• Known channelopathy such as Brugada syndrome, long QT syndrome, or Catecholaminergic monomorphic ventricular tachycardia.
• Episodic or permanent complete heart block or 2nd degree atrioventricular block Mobitz 2 or bifascicular block with concurrent 1st degree atrioventricular block
• Congestive heart failure New York Heart Association class IV, defined as shortness of breath at rest, which is refractory to medical treatment (not responding to treatment)
• Inability to comply with the protocol.

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Study Record Dates

• First Submitted: August 1, 2025
• First Posted: September 9, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: September 9, 2025

Record last verified: 2025-08