Postural Tachycardia SyndromePhase 1NCT03124355
Vagal Stimulation in POTS
A Phase 1 study testing Pyridostigmine Pill, Galantamine Pill and Vagal stimulation in people with Postural Tachycardia Syndrome, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to investigate how the electrical stimulation of a nerve in the skin of the earlobe (transcutaneous vagal nerve stimulation), alone or in combination with two medications (galantamine and pyridostigmine), affects the way the autonomic (involuntary) nervous system controls heart rhythm… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Postural Tachycardia Syndrome
- What is being tested?
- Pyridostigmine Pill, Galantamine Pill and Vagal stimulation
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2017to Dec 2027
- Phase
- Phase 1
- 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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Female subjects of 18-45 years, with Postural Tachycardia Syndrome (POTS) as defined by a heart rate increase ≥30 bpm from supine within 10 min of standing or head-up tilt in the absence of orthostatic hypotension, with chronic symptoms (> 6 months), and in the absence of other acute cause of orthostatic tachycardia.
- Subjects able and willing to provide informed consent
Who cannot join
- Pregnancy.
- Medical conditions that can explain postural tachycardia (e.g., dehydration, medications).
- Patients who are bedridden or chair-ridden
- Subjects taking any medication known to affect autonomic function or inflammatory markers (e.g. corticosteroids) who could not discontinue them before study participation.
- Conditions associated with chronic inflammatory processes which in the investigator's opinion would affect the interpretation of the results. Examples may include smoking, diabetes, BMI>30 kg/m2, current infections or cancer.
- Other factors which in the investigator's opinion would prevent the subject from completing the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Autonomic Dysfunction Center/ Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Vagal Stimulation in POTS - The Autonomic Inflammatory Reflex (Pilot 3)
The purpose of this study is to investigate how the electrical stimulation of a nerve in the skin of the earlobe (transcutaneous vagal nerve stimulation), alone or in combination with two medications (galantamine and pyridostigmine), affects the way the autonomic (involuntary) nervous system controls heart rhythm, symptoms on standing, and inflammatory markers in female patients with postural tachycardia syndrome (POTS). The study consists of 2 parts: a screening (1-2 study days), and 3 testing days. The study will take 5 days total and about 16 participants will be screened for the study. The investigators estimate 13 will be eligible to participate in all of the study days.
Read the detailed description
This study will test the hypothesis that impairment of the parasympathetic nervous system contributes to the symptoms of POTS and that stimulation of this part of the nervous system improves the excessive increase in heart rate, standing tolerance and inflammation in patients with POTS. For this purpose, the investigators will use electrical stimulation of a nerve in the skin of the earlobe (transcutaneous vagal nerve stimulation) and two medications that increase the levels of acetylcholine (a neurotransmitter) in the central or peripheral nervous system (galantamine and pyridostigmine, respectively) to increase the activity of the parasympathetic nervous system.
Screening Procedures: Potential participants will be screened in the Vanderbilt Autonomic Dysfunction Center (ADC). Medications affecting heart rate, blood pressure, blood volume, inflammatory markers and the autonomic nervous system will be withdrawn for at least five half-lives before studies. Patients will undergo a complete history and physical examination, ECG, routine clinical laboratory analyses and a blood pregnancy test for women of childbearing potential. Autonomic testing including a posture study with plasma catecholamines is then performed to determine if they meet the inclusion/exclusion criteria.
Eligible participants will be studied on three separate days in a randomized, double-blind, crossover fashion. On each testing day, patients will be given one dose of the study medication (either pyridostigmine, galantamine or placebo pill), and then will have two tilt table tests (a motorized table with a footboard that moves to an upright position): one with the vagal stimulation and one with sham electrical stimulation. Heart rhythm, blood pressure and the amount of fluid in the body (body impedance) will be monitored during studies. Blood samples (up to a total of 2 tablespoons per study day) will also be collected. The order of the study days and tilt tests will be decided at random, like the toss of a coin. Each study day will last about 5 hours.
- Conditions
- Postural Tachycardia Syndrome
- Being tested
- placebo sugar pill, Pyridostigmine Pill, Galantamine Pill, Vagal stimulation, Sham vagal stimulation
- Keywords
- vagal stimulation, POTS, galantamine, pyridostigmine
- 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.
placebo sugar pillDrug
Also called placebo
placebo single oral dose
Pyridostigmine PillDrug
Also called pyridostigmine bromide, Mestinon
pyridostigmine bromide 30 mg single oral dose
Galantamine PillDrug
Also called Galantamine hydrobromide, Razadyne
Galantamine hydrobromide 8mg single oral dose
Vagal stimulationDevice
Also called Transcutaneous vagal nerve stimulation
Vagal stimulation will be given at 50 Hz during the tilt table tests
Sham vagal stimulationDevice
Sham vagal stimulation will be given at 0.01 mA during the tilt table tests
| Study group | Role | What they receive |
|---|---|---|
| Placebo pill with vagal/sham stimulation | Experimental | Patients will receive a single oral dose of placebo sugar pill, and 1.5-2 hours later they will have two tilt table tests: one with vagal stimulation and one with sham vagal stimulation Receives: Drug: placebo sugar pill; Device: Vagal stimulation; Device: Sham vagal stimulation |
| Pyridostigmine with vagal/sham stimulation | Experimental | Patients will receive a single oral dose of pyridostigmine pill 30 mg, and 1.5-2 hours later they will have two tilt table tests: one with vagal stimulation and one with sham vagal stimulation Receives: Drug: Pyridostigmine Pill; Device: Vagal stimulation; Device: Sham vagal stimulation |
| Galantamine with vagal/sham stimulation | Experimental | Patients will receive a single oral dose of galantamine pill 8 mg, and 1.5-2 hours later they will have two tilt table tests:one with vagal stimulation and one with sham vagal stimulation Receives: Drug: Galantamine Pill; Device: Vagal stimulation; Device: Sham vagal stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
High frequency variability of heart rate
Average of high frequency variability of heart rate during the head up tilt
Measured: Up to 15 min of head up tilt
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2017
- Study start30 Sep 2017
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postural Tachycardia SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, double-blind, crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Italo Biaggioni, Vanderbilt University Medical Center
- Investigators
- Italo Biaggioni, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03124355
- Sponsor's protocol ID
- 6111
- Status last verified
- Jul 2026
- First submitted
- 18 Apr 2017
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vagal Stimulation in POTS - The Autonomic Inflammatory Reflex (Pilot 3)
- ClinicalTrials.gov ID
- NCT03124355
- Acronym / sponsor ID
- 6111
- Conditions
- Postural Tachycardia Syndrome
- Keywords
- vagal stimulation, POTS, galantamine, pyridostigmine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 30 Sep 2017 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 21 Apr 2017 (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.
The purpose of this study is to investigate how the electrical stimulation of a nerve in the skin of the earlobe (transcutaneous vagal nerve stimulation), alone or in combination with two medications (galantamine and pyridostigmine), affects the way the autonomic (involuntary) nervous system controls heart rhythm, symptoms on standing, and inflammatory markers in female patients with postural tachycardia syndrome (POTS). The study consists of 2 parts: a screening (1-2 study days), and 3 testing days. The study will take 5 days total and about 16 participants will be screened for the study. The investigators estimate 13 will be eligible to participate in all of the study days.
Detailed description
This study will test the hypothesis that impairment of the parasympathetic nervous system contributes to the symptoms of POTS and that stimulation of this part of the nervous system improves the excessive increase in heart rate, standing tolerance and inflammation in patients with POTS. For this purpose, the investigators will use electrical stimulation of a nerve in the skin of the earlobe (transcutaneous vagal nerve stimulation) and two medications that increase the levels of acetylcholine (a neurotransmitter) in the central or peripheral nervous system (galantamine and pyridostigmine, respectively) to increase the activity of the parasympathetic nervous system.
Screening Procedures: Potential participants will be screened in the Vanderbilt Autonomic Dysfunction Center (ADC). Medications affecting heart rate, blood pressure, blood volume, inflammatory markers and the autonomic nervous system will be withdrawn for at least five half-lives before studies. Patients will undergo a complete history and physical examination, ECG, routine clinical laboratory analyses and a blood pregnancy test for women of childbearing potential. Autonomic testing including a posture study with plasma catecholamines is then performed to determine if they meet the inclusion/exclusion criteria.
Eligible participants will be studied on three separate days in a randomized, double-blind, crossover fashion. On each testing day, patients will be given one dose of the study medication (either pyridostigmine, galantamine or placebo pill), and then will have two tilt table tests (a motorized table with a footboard that moves to an upright position): one with the vagal stimulation and one with sham electrical stimulation. Heart rhythm, blood pressure and the amount of fluid in the body (body impedance) will be monitored during studies. Blood samples (up to a total of 2 tablespoons per study day) will also be collected. The order of the study days and tilt tests will be decided at random, like the toss of a coin. Each study day will last about 5 hours.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Randomized, double-blind, crossover
| Arm | Type | Receives |
|---|---|---|
| Placebo pill with vagal/sham stimulation | Experimental | Drug: placebo sugar pill, Device: Vagal stimulation, Device: Sham vagal stimulationPatients will receive a single oral dose of placebo sugar pill, and 1.5-2 hours later they will have two tilt table tests: one with vagal stimulation and one with sham vagal stimulation |
| Pyridostigmine with vagal/sham stimulation | Experimental | Drug: Pyridostigmine Pill, Device: Vagal stimulation, Device: Sham vagal stimulationPatients will receive a single oral dose of pyridostigmine pill 30 mg, and 1.5-2 hours later they will have two tilt table tests: one with vagal stimulation and one with sham vagal stimulation |
| Galantamine with vagal/sham stimulation | Experimental | Drug: Galantamine Pill, Device: Vagal stimulation, Device: Sham vagal stimulationPatients will receive a single oral dose of galantamine pill 8 mg, and 1.5-2 hours later they will have two tilt table tests:one with vagal stimulation and one with sham vagal stimulation |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Female subjects of 18-45 years, with Postural Tachycardia Syndrome (POTS) as defined by a heart rate increase ≥30 bpm from supine within 10 min of standing or head-up tilt in the absence of orthostatic hypotension, with chronic symptoms (> 6 months), and in the absence of other acute cause of orthostatic tachycardia.
- Subjects able and willing to provide informed consent
Key exclusion criteria (6 listed)
- Pregnancy.
- Medical conditions that can explain postural tachycardia (e.g., dehydration, medications).
- Patients who are bedridden or chair-ridden
- Subjects taking any medication known to affect autonomic function or inflammatory markers (e.g. corticosteroids) who could not discontinue them before study participation.
- Conditions associated with chronic inflammatory processes which in the investigator's opinion would affect the interpretation of the results. Examples may include smoking, diabetes, BMI>30 kg/m2, current infections or cancer.
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 |
|---|---|---|
| placebo sugar pillAlso: placeboplacebo single oral dose | Drug | Placebo pill with vagal/sham stimulation |
| Pyridostigmine PillAlso: pyridostigmine bromide, Mestinonpyridostigmine bromide 30 mg single oral dose | Drug | Pyridostigmine with vagal/sham stimulation |
| Galantamine PillAlso: Galantamine hydrobromide, RazadyneGalantamine hydrobromide 8mg single oral dose | Drug | Galantamine with vagal/sham stimulation |
| Vagal stimulationAlso: Transcutaneous vagal nerve stimulationVagal stimulation will be given at 50 Hz during the tilt table tests | Device | Galantamine with vagal/sham stimulation, Placebo pill with vagal/sham stimulation, Pyridostigmine with vagal/sham stimulation |
| Sham vagal stimulationSham vagal stimulation will be given at 0.01 mA during the tilt table tests | Device | Galantamine with vagal/sham stimulation, Placebo pill with vagal/sham stimulation, Pyridostigmine with vagal/sham stimulation |
Primary outcome
High frequency variability of heart rate
Time frame: Up to 15 min of head up tilt
Average of high frequency variability of heart rate during the head up tilt
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 13 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for Postural Tachycardia Syndrome
Enrolling by invitationObservational study
Presentation of Young Adults With and Without Joint Hypermobility
Hypermobile Ehlers-Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome (POTS)
Active, not recruiting
Acute Salt Handling in Orthostatic Intolerance
Postural Tachycardia Syndrome, Orthostatic Tachycardia
Active, not recruitingPhase 1/2
Treatment of Orthostatic Intolerance
Tachycardia, Chronic Orthostatic Intolerance
Active, not recruiting
Intravenous (IV) Saline and Exercise in Postural Tachycardia Syndrome (POTS)
Postural Tachycardia Syndrome
Active, not recruitingObservational study
Sleep Actigraphy in Postural Tachycardia Syndrome (POTS)
Postural Tachycardia Syndrome, Orthostatic Intolerance
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. This study is not recruiting at the moment.
Italo Biaggioni, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pyridostigmine Pill, Galantamine Pill and Vagal stimulation in people with Postural Tachycardia Syndrome, run by Vanderbilt University Medical Center at 1 site in United States.
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 2 inclusion and 6 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: under way, not looking for participants, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
High frequency variability of heart rate (time frame: Up to 15 min of head up tilt). 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 13 Jul 2026.