This study investigates a non-pharmacological treatment approach for Postural OrthostaticTachycardia Syndrome (POTS), a disorder of the autonomic nervous system characterized byan excessive increase in heart rate upon standing. POTS is commonly associated withsymptoms such as dizziness, fatigue, cognitive difficulties, sleep disturbances, as wellas anxiety and depression, which significantly impair quality of life.This randomized, controlled clinical trial aims to evaluate whether combiningtranscutaneous auricular vagus nerve stimulation (taVNS) with slow-paced diaphragmaticbreathing (at 0.1 Hz) provides greater therapeutic benefit compared to taVNS alone orsham 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, orsham 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 theintervention, including measurements of heart rate, inflammatory cytokines, andpatient-reported outcomes on sleep, mood, and quality of life.The study is conducted at the Center for Public Health, Medical University of Vienna, andis open to individuals diagnosed with POTS, including those with coexisting Post-COVID-19syndrome.
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.
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 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 without Breathing Training (TVNS+NB)
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: Sham TVNS + SDB
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 + NB
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.
Inclusion Criteria:
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 informed consent.
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 informed consent.
Not Provided
Ali Kapan, PhD
+43 01 40160 34608
ali.kapan@meduniwien.ac.at
Ali Kapan, PhD, Principal Investigator
Medical University of Vienna, Center for Public Health,