An interventional study of TVNS + Slow-Paced Breathing (TVNS+SDB) and TVNS without Breathing Training (TVNS+NB) in Postural Orthostatic Tachycardia Syndrome (POTS) and Post-acute COVID-19 Syndromes, sponsored by Ali Kapan. Not yet recruiting. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-06-04.
Sponsored by Ali Kapan · Not applicable, Interventional, and Treatment
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This study investigates a non-pharmacological treatment approach for Postural Orthostatic Tachycardia Syndrome (POTS), a disorder of the autonomic nervous system characterized by an excessive increase in heart rate upon standing. POTS is commonly associated with symptoms such as dizziness, fatigue, cognitive difficulties, sleep disturbances, as well as anxiety and depression, which significantly impair quality of life.
This randomized, controlled clinical trial aims to evaluate whether combining transcutaneous auricular vagus nerve stimulation (taVNS) with slow-paced diaphragmatic breathing (at 0.1 Hz) provides greater therapeutic benefit compared to taVNS alone or sham stimulation.
A total of 100 participants will be recruited and randomly assigned to one of four groups (25 per group):
taVNS with slow-paced breathing,
taVNS with spontaneous (normal) breathing,
sham taVNS with slow-paced breathing, or
sham taVNS with spontaneous breathing.
Participants will perform the intervention daily at home for a duration of 12 weeks. Medical and psychological assessments will be conducted before and after the intervention, including measurements of heart rate, inflammatory cytokines, and patient-reported outcomes on sleep, mood, and quality of life.
The study is conducted at the Center for Public Health, Medical University of Vienna, and is open to individuals diagnosed with POTS, including those with coexisting Post-COVID-19 syndrome.
Postural Orthostatic Tachycardia Syndrome (POTS) is a disorder of the autonomic nervous system characterized by an excessive increase in heart rate (≥30 bpm) within 10 minutes of standing, without a significant drop in blood pressure. Affected individuals frequently suffer from fatigue, dizziness, palpitations, cognitive dysfunction ("brain fog"), anxiety, depression, and sleep disturbances. These symptoms significantly impair daily functioning and quality of life.
Conventional pharmacological treatments often yield limited benefit and can lead to adverse effects, especially in individuals with complex autonomic dysregulation. Non-pharmacological approaches that target the autonomic nervous system more holistically and with fewer side effects are gaining increasing scientific interest.
This randomized, controlled clinical trial aims to investigate the effects of combining transcutaneous auricular vagus nerve stimulation (taVNS) with slow-paced diaphragmatic breathing at 0.1 Hz (six breaths per minute) as an integrative therapeutic strategy for individuals with POTS.
A total of 100 participants diagnosed with POTS will be randomly assigned (1:1:1:1) into four groups (25 per group):
taVNS combined with slow-paced diaphragmatic breathing (0.1 Hz)
taVNS combined with spontaneous breathing (no guided breathing exercises)
sham taVNS combined with slow-paced diaphragmatic breathing (0.1 Hz)
sham taVNS combined with spontaneous breathing (no guided breathing exercises)
All participants will undergo standardized instruction in the use of the stimulation device and, where applicable, in breathing technique by a trained therapist. The intervention will be performed daily at home for 12 weeks. taVNS is administered for 60 minutes per session using a CE-certified medical device (Nurosym™), with stimulation parameters set at 20 Hz and 200 µs pulse width. For those in the breathing groups, the slow-paced breathing is guided via a mobile app and performed for 10 minutes in the first 4 weeks and 15 minutes in the final weeks.
To evaluate the intervention's effects, a comprehensive set of physiological and psychological parameters will be assessed before and after the 12-week intervention period, including:
Change in heart rate response to orthostatic challenge (Tilt Test)
Capnography (end-tidal CO₂ monitoring) during the Tilt Test to assess ventilatory compensation and respiratory dysregulation
Cerebral tissue oxygenation measured by near-infrared spectroscopy (NIRS) during orthostatic testing to evaluate cerebral perfusion
Heart rate variability (HRV)
Serum levels of inflammatory cytokines (TNF-α, IL-6, IL-8, CRP)
Self-reported symptom burden (Malmö POTS Symptom Score)
Sleep quality (PSQI)
Health-related quality of life (SF-36)
Psychological distress (DASS-21)
Daily activity and resting heart rate (7-day wearable device)
Handgrip strength as a marker of physical capacity
Participants will also be monitored for adherence and potential adverse events. The sham taVNS groups will use identical devices delivering subthreshold stimulation to maintain blinding.
The study is conducted at the Center for Public Health, Medical University of Vienna. Eligible participants must have a confirmed diagnosis of POTS, with or without post-COVID syndrome, and meet the study's inclusion criteria. Randomization is stratified by sex and post-COVID status to ensure balance across treatment arms.
This trial aims to determine whether the integrative approach of vagal stimulation and paced breathing can enhance autonomic regulation, improve cerebral perfusion, reduce inflammation, and improve psychological outcomes in individuals with POTS. The results may offer an evidence-based foundation for non-invasive neuromodulation in the management of autonomic disorders.
136 studies on the registry are indexed under Postural Orthostatic Tachycardia Syndrome; 42 are open to participants now.
This study's planned enrollment of 100 is above the median of 36 across 102 interventional studies indexed under Postural Orthostatic Tachycardia Syndrome.
Browse Postural Orthostatic Tachycardia Syndrome studies →This is the only study on the registry with Ali Kapan as lead sponsor.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Formal diagnosis of Postural Orthostatic Tachycardia Syndrome (POTS), confirmed by clinical criteria: a sustained increase in heart rate (HR) of ≥30 bpm within 10 minutes of standing, without orthostatic hypotension.
History of POTS diagnosis for at least 6 months.
Participants with Post-acute COVID-19 syndrome may be included if they meet the formal POTS criteria. These participants will be stratified based on the presence or absence of Post-Exertional Malaise (PEM).
Stable medication for POTS (same dosage/class) for at least 4 weeks before enrollment.
Willingness and ability to provide .
Screening of Undiagnosed Participants:
Suspected POTS based on clinical symptoms (e.g., dizziness, fatigue, syncope, brain fog, palpitations, exercise intolerance) persisting ≥6 months.
Preliminary Schellong test by study team.
If criteria are met, referral to a specialist (neurology or cardiology) for diagnostic confirmation.
Inclusion only after specialist-confirmed POTS diagnosis.
Exclusion Criteria:
Significant hypertension (BP >150/100 mmHg supine or standing).
Orthostatic hypotension: drop in BP >20 mmHg systolic or >10 mmHg diastolic upon standing.
Recent stroke or myocardial infarction (within 6 months).
Significant immunological or hematological disorders.
Severe anemia (hematocrit \<28%).
History of vagotomy.
Pregnancy or lactation.
Inability or unwillingness to provide .
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive active transcutaneous auricular vagus nerve stimulation (taVNS) using electrodes placed at the cymba conchae, combined with guided slow-paced diaphragmatic breathing (0.1 Hz). The intervention is performed daily at home for 12 weeks, with each session lasting 60 minutes.
Device: TVNS + Slow-Paced Breathing (TVNS+SDB)
Participants receive active transcutaneous auricular vagus nerve stimulation (taVNS) using electrodes placed at the cymba conchae, combined with spontaneous breathing (no guided breathing exercises). The intervention is performed daily at home for 12 weeks, with each session lasting 60 minutes.
Device: TVNS without Breathing Training (TVNS+NB)
Participants receive transcutaneous auricular vagus nerve stimulation using a sham protocol via electrodes placed at the cymba conchae, combined with guided slow-paced diaphragmatic breathing (0.1 Hz). The intervention is performed daily at home for 12 weeks, with each session lasting 60 minutes.
Device: Sham TVNS + SDB
Participants receive transcutaneous auricular vagus nerve stimulation using a sham protocol via electrodes placed at the cymba conchae, combined with spontaneous breathing (no guided breathing exercises). The intervention is performed daily at home for 12 weeks, with each session lasting 60 minutes.
Device: Sham TVNS + NB
Participants receive active transcutaneous auricular vagus nerve stimulation (taVNS) using electrodes placed at the cymba conchae, combined with guided slow-paced diaphragmatic breathing (0.1 Hz). The intervention is performed daily at home for 12 weeks, with each session lasting 60 minutes.
Participants receive active transcutaneous auricular vagus nerve stimulation (taVNS) using electrodes placed at the cymba conchae, combined with spontaneous breathing (no guided breathing exercises). The intervention is performed daily at home for 12 weeks, with each session lasting 60 minutes.
Participants receive transcutaneous auricular vagus nerve stimulation using a sham protocol via electrodes placed at the cymba conchae, combined with guided slow-paced diaphragmatic breathing (0.1 Hz). The intervention is performed daily at home for 12 weeks, with each session lasting 60 minutes.
Participants receive transcutaneous auricular vagus nerve stimulation using a sham protocol via electrodes placed at the cymba conchae, combined with spontaneous breathing (no guided breathing exercises). The intervention is performed daily at home for 12 weeks, with each session lasting 60 minutes.
Change in Heart Rate From Supine to Standing (Delta HR) After 12 Weeks of Daily taVNS With or Without Slow-Paced Breathing in Individuals With POTS
Heart rate (HR) is continuously recorded via 12-lead ECG during a standardized Tilt test. Participants lie supine for 25 minutes and then stand upright for 10 minutes. The average HR from the last 10 minutes supine and the 10-minute standing phase is calculated. The primary outcome, Delta HR, is defined as the difference between upright and supine HR. This measure reflects autonomic cardiovascular response and is assessed before and after the 12-week intervention phase.
Time frame: Change in Heart Rate (Delta HR) from Supine to Standing at Baseline and Week 12
No study locations are listed for this record.
Plan to share: No — Individual participant data (IPD) will not be shared with other researchers. According to the informed consent and data protection requirements, data may only be used within the study and by authorized parties. No data will be shared outside the study team or transferred to third parties, including for secondary analysis or outside the EU.
Start is estimated for Sep 2025; primary completion for Mar 2028, 30 months later.
Of 44 non-industry interventional studies with no phase under Postural Orthostatic Tachycardia Syndrome, half reached primary completion within 46 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 61. This study's planned 30 months is below that.
Counting every sponsor, half of 44 studies reached it within 46 months; a quarter within 20 and three quarters within 61.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in May 2025. You cannot join it, but the record below documents what was studied.
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Postural Orthostatic Tachycardia Syndrome →