Postural Orthostatic Tachycardia Syndrome (POTS)TREAT-POTSNCT07163130
Tragus Stimulation for POTS Treatment
A study testing Transcutaneous auricular vagus nerve stimulation in people with Postural Orthostatic Tachycardia Syndrome (POTS), run by Aristotle University Of Thessaloniki.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Postural Orthostatic Tachycardia Syndrome (POTS)
- What is being tested?
- Transcutaneous auricular vagus nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2025to 31 Jan 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
About this study
Official title: Transcutaneous Auricular Vagus Nerve Stimulation in Postural Tachycardia Syndrome: a Prospective Cross-over Study
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.
- Being tested
- Transcutaneous auricular vagus nerve stimulation
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous auricular vagus nerve stimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment sequence: Active - Sham | Other | This arm will undergo active treatment first and then (after a wash-out period) sham treatment. Receives: 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 Receives: Device: Transcutaneous auricular vagus nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Through study completion, up to 16 months from study start date
Secondary outcomes (1)
Autonomic symptoms assessed using the Malmo POTS Score questionnaire
Measured: Through study completion, up to 16 months from study start date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2025
- Study start1 Sep 2025 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postural Orthostatic Tachycardia Syndrome (POTS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vassilios Vassilikos, Aristotle University Of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07163130
- Sponsor's protocol ID
- TREATPOTS3RDCARDIO
- Acronym
- TREAT-POTS
- Status last verified
- Aug 2025
- First submitted
- 1 Aug 2025
- Last updated
- 9 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Auricular Vagus Nerve Stimulation in Postural Tachycardia Syndrome: a Prospective Cross-over Study
- ClinicalTrials.gov ID
- NCT07163130
- Acronym / sponsor ID
- TREAT-POTS / TREATPOTS3RDCARDIO
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- 1 Sep 2025 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 9 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment sequence: Active - Sham | Other | Device: Transcutaneous auricular vagus nerve stimulationThis arm will undergo active treatment first and then (after a wash-out period) sham treatment. |
| Treatment sequence: Sham - Active | Other | Device: Transcutaneous auricular vagus nerve stimulationThis arm will undergo sham treatment first and then (after a wash-out period) active treatment |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous auricular vagus nerve stimulationTranscutaneous 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. | Device | Treatment sequence: Active - Sham, Treatment sequence: Sham - Active |
Primary outcome
Difference in Heart Rate change during the posture test, between the 2 treatment periods (on-treatment versus off-treatment).
Time frame: Through study completion, up to 16 months from study start date
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).
1 secondary outcome
Autonomic symptoms assessed using the Malmo POTS Score questionnaire
Time frame: Through study completion, up to 16 months from study start date
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous auricular vagus nerve stimulation in people with Postural Orthostatic Tachycardia Syndrome (POTS), run by Aristotle University Of Thessaloniki.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Heart Rate change during the posture test, between the 2 treatment periods (on-treatment versus off-treatment). (time frame: Through study completion, up to 16 months from study start date). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2025.