NCT06996314

Brief Summary

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.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for not_applicable

Timeline
29mo left

Started Sep 2025

Typical duration for not_applicable

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress23%
Sep 2025Aug 2028

First Submitted

Initial submission to the registry

May 21, 2025

Completed
9 days until next milestone

First Posted

Study publicly available on registry

May 30, 2025

Completed
3 months until next milestone

Study Start

First participant enrolled

September 1, 2025

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2028

Last Updated

June 4, 2025

Status Verified

May 1, 2025

Enrollment Period

2.5 years

First QC Date

May 21, 2025

Last Update Submit

May 30, 2025

Conditions

Postural Orthostatic Tachycardia Syndrome (POTS)Post-acute COVID-19 Syndromes

Outcome Measures

Primary Outcomes (1)

  • 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.

    Change in Heart Rate (Delta HR) from Supine to Standing at Baseline and Week 12

Study Arms (4)

TVNS + Slow-Paced Breathing (TVNS+SDB)

ACTIVE COMPARATOR

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)

TVNS without Breathing Training (TVNS+NB)

ACTIVE COMPARATOR

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)

Sham TVNS + SDB

ACTIVE COMPARATOR

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

Sham TVNS + NB

SHAM COMPARATOR

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

Interventions

TVNS + Slow-Paced Breathing (TVNS+SDB)DEVICE

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.

TVNS + Slow-Paced Breathing (TVNS+SDB)
TVNS without Breathing Training (TVNS+NB)DEVICE

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.

TVNS without Breathing Training (TVNS+NB)
Sham TVNS + SDBDEVICE

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.

Sham TVNS + SDB
Sham TVNS + NBDEVICE

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.

Sham TVNS + NB

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Links

MeSH Terms

Conditions

Postural Orthostatic Tachycardia SyndromePost-Acute COVID-19 Syndrome

Condition Hierarchy (Ancestors)

Orthostatic IntolerancePrimary DysautonomiasAutonomic Nervous System DiseasesNervous System DiseasesCOVID-19Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract DiseasesPost-Infectious DisordersChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Ali Kapan, PhD

    Medical University of Vienna, Center for Public Health,

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ali Kapan, PhD

CONTACT

+43 01 40160 34608ali.kapan@meduniwien.ac.at

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

May 21, 2025

First Posted

May 30, 2025

Study Start

September 1, 2025

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

August 31, 2028

Last Updated

June 4, 2025

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will not share

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.