Postural Orthostatic Tachycardia SyndromeNCT02725060
Autoimmune Basis for Postural Tachycardia Syndrome
A study testing phenylephrine, isoproterenol and 25 micro-Ci of radiation in people with Postural Orthostatic Tachycardia Syndrome and Postural Tachycardia Syndrome, run by Vanderbilt University Medical Center at 2 sites in United States.
Trial summary
The purpose of this study is to see if some people with postural tachycardia syndrome (POTS) have higher levels of immune proteins (autoantibodies) directed against receptors of the autonomic nervous system, and if these autoantibodies make a difference in their POTS symptoms. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, Tachycardia
- What is being tested?
- phenylephrine, isoproterenol and 25 micro-Ci of radiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2016to Dec 2026
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-50 years old
- Postural Tachycardia Syndrome: Heart rate increase >30 bpm from supine within 10 min of standing, in the absence of orthostatic hypotension (>20/10 mmHg fall in blood pressure), with chronic symptoms (> 6 months), and in the absence of other acute cause of orthostatic tachycardia.
- Able and willing to provide informed consent
- Female premenopausal subjects must utilize adequate birth control and willingness to undergo serum beta-hCG testing
- The subject must understand and be able to comply with the study procedures and restrictions.
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 stand)
- Pregnancy
- Cardiovascular disease, such as myocardial infarction within 6 months, angina pectoris, significant arrhythmia (sinus tachycardia is not excluded), deep vein thrombosis, pulmonary embolism
- History of serious neurologic disease
- History or presence of significant immunological or hematological disorders
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- Clinically significant gastrointestinal impairment that could interfere with dietary compliance or drug absorption
- Impaired hepatic function (aspartate amino transaminase and/or alanine amino transaminase >1.5 x upper limit of normal range)
- Impaired renal function (serum creatinine >1.5 mg/dL)
- Hematocrit <28%
- Current or concurrent disease that could affect the absorption, action or disposition of the drug, or clinical or laboratory assessments.
- Any underlying or acute disease requiring regular medication that could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
- Inability to comply with the protocol
- Healthy control subjects will be healthy, non-smoking and on no chronic medications at the time of the study. Healthy control subjects will be group-matched to the POTS patients for age and gender. We will attempt to study female patients in the first half of their menstrual cycle to minimize cyclical variability.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites
Autonomic Dysfunction Center
Nashville, Tennessee, 37232
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73117-1213
About this study
The purpose of this study is to see if some people with postural tachycardia syndrome (POTS) have higher levels of immune proteins (autoantibodies) directed against receptors of the autonomic nervous system, and if these autoantibodies make a difference in their POTS symptoms. The investigators also want to see if the levels of these autoantibodies stay the same over time.
Read the detailed description
Postural tachycardia syndrome (POTS) is a debilitating disorder resulting from cardiovascular autonomic dysfunction, has many causes and is very difficult to treat effectively. The investigators have identified the presence of autoantibodies (immune proteins) directed against some receptors of the autonomic nervous system that can cause patient's symptoms on standing.
The present study is designed to test the hypothesis that patients with POTS harbor functional autoantibodies to adrenergic receptors that lead to an excessive tachycardia characteristic of POTS. For this purpose, this study will define the prevalence, burden, and the in vivo physiological significance of these adrenergic antibodies in a well-phenotyped and representative cohort of patients with POTS and a matched cohort of healthy control subjects, and will characterize the stability of these autoantibodies over time in affected POTS patients.
- Conditions
- Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, Tachycardia, Arrhythmias, Cardiac, Autonomic Nervous System Diseases, Orthostatic Intolerance
- Being tested
- phenylephrine, isoproterenol, 25 micro-Ci of radiation, Posture study with blood samples, 24-hour heart rhythm and blood pressure monitoring
- Keywords
- POTS, Orthostatic Intolerance, Orthostatic Tachycardia
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome, Tachycardia, Arrhythmias, Cardiac, Autonomic Nervous System Diseases, Orthostatic Intolerance, Cardiovascular Diseases, Primary Dysautonomias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phenylephrineDrug
Phenylephrine is a selective α1-adrenergic receptor agonist. It will be given in IV bolus injections starting from 12.5 ug. Incremental doses will be given every ~3 min up to 800 ug or until systolic blood pressure increases by 25 mmHg
isoproterenolDrug
Also called isuprel, isoprenaline
Isoproterenol is non-selective beta-adrenergic agonist. It will be given in IV bolus injections starting from 0.025 ug. Incremental doses will be given every ~3 min until heart rate increases by 25 bpm. This intervention is optional.
25 micro-Ci of radiationRadiation
Also called DAXOR
Using injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation, blood samples are drawn before and 30 minutes after injection.
Posture study with blood samplesProcedure or surgery
Also called orthostatic challenge, orthostatic stress test
Blood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes. Blood will be drawn in each position to measure hormones that regulate blood pressure and blood volume. An additional sample will be collected in the supine position for the autoantibody assessment.
24-hour heart rhythm and blood pressure monitoringProcedure or surgery
Also called 24 Holter
Blood pressure, heart rate and ECG monitoring for 24 hours
Quantitative Axonal Sudomotor Reflex TestingProcedure or surgery
Also called QSART, sweat test
The QSART assesses the ability of sympathetic nerve terminals in the skin to release acetylcholine and increase sweat production. The test is performed at 4 sites over the forearm, proximal lateral leg, medial distal leg and proximal foot.
Autonomic function testsProcedure or surgery
The autonomic function tests will determine how well the autonomic nervous system regulates blood pressure and heart rate. These tests include breathing deeply for two minutes, breathing fast for 30 seconds, maintaining a handgrip for 3 minutes, breathing against pressure for 15 seconds, and placing the hand in ice water for 1 minute. In addition, participants will be tilted up on a tilt table for up to 10 minutes while recording their heart rate, blood pressure and cardiac output.
Rebreathing testOther
Also called cardiac output measurement
Cardiac output will be measured using the rebreathing technique (Innocor)
Assessment of splanchnic capacitanceOther
Splanchnic capacitance will be assessed using cpap and body impedance to construct pressure volume curves
microneurographyProcedure or surgery
Also called msna
microneurography will be measured in the peroneal nerve to assess sympathetic activity.
| Study group | Role | What they receive |
|---|---|---|
| Autonomic and Antibody Assessments | Experimental | On up to 3 study days, POTS patients and control subjects will have several tests to assess autonomic function and to detect the presence of autoantibodies to adrenergic receptors. The following tests will de done but in some participants it may not be necessary to do all of them. The investigator will discuss with each participant which particular tests will be done in each particular case:
* Posture study with blood samples for autoantibody testing
* 24-hour heart rhythm and blood pressure monitoring
* autonomic function tests
* Quantitative Axonal Sudomotor Reflex Testing
* Total blood volume assessment
* Pharmacologic testing with phenylephrine
* Pharmacologic testing with isoproterenol
* Cardiac output with rebreathing
* Assessment of splanchnic capacitance
* Microneurography Receives: Drug: phenylephrine; Drug: isoproterenol; Radiation: 25 micro-Ci of radiation; Procedure: Posture study with blood samples; Procedure: 24-hour heart rhythm and blood pressure monitoring; Procedure: Quantitative Axonal Sudomotor Reflex Testing; Procedure: Autonomic function tests; Other: Rebreathing test; Other: Assessment of splanchnic capacitance; Procedure: microneurography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Autoantibody levels
Blood samples collected while supine during the posture study will be analyzed for autoantibody positivity in POTS patients and control subjects.
Measured: up to 10 minutes
Blood pressure after phenylephrine boluses
Measured: 1-2 minutes after bolus injections
Heart rate after isoproterenol boluses
Measured: 1-2 minutes after bolus injections
Orthostatic change in heart rate
Difference between standing and supine heart rates.
Measured: up to 10 minutes
Secondary outcomes (2)
Blood pressure response during phase IV of the Valsalva maneuver
Measured: up to 10 minutes
Hear rate response during phase IV of the Valsalva maneuver
Measured: up to 10 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2016 (estimated)
- Study startFeb 2016
- Primary completionOct 2026 (estimated)
- Study completionDec 2026 (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 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 N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oklahoma
- Responsible party
- Principal investigator, Luis E Okamoto, Vanderbilt University Medical Center
- Investigators
- Luis Okamoto, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02725060
- Sponsor's protocol ID
- 151791
- Status last verified
- Nov 2025
- First submitted
- 22 Feb 2016
- Last updated
- 12 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autoimmune Basis for Postural Tachycardia Syndrome
- ClinicalTrials.gov ID
- NCT02725060
- Acronym / sponsor ID
- 151791
- Conditions
- Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, Tachycardia, Arrhythmias, Cardiac, Autonomic Nervous System Diseases, Orthostatic Intolerance
- Keywords
- POTS, Orthostatic Intolerance, Orthostatic Tachycardia
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- University of Oklahoma
- Study start
- Feb 2016 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 31 Mar 2016 (estimated)
- 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 see if some people with postural tachycardia syndrome (POTS) have higher levels of immune proteins (autoantibodies) directed against receptors of the autonomic nervous system, and if these autoantibodies make a difference in their POTS symptoms. The investigators also want to see if the levels of these autoantibodies stay the same over time.
Detailed description
Postural tachycardia syndrome (POTS) is a debilitating disorder resulting from cardiovascular autonomic dysfunction, has many causes and is very difficult to treat effectively. The investigators have identified the presence of autoantibodies (immune proteins) directed against some receptors of the autonomic nervous system that can cause patient's symptoms on standing.
The present study is designed to test the hypothesis that patients with POTS harbor functional autoantibodies to adrenergic receptors that lead to an excessive tachycardia characteristic of POTS. For this purpose, this study will define the prevalence, burden, and the in vivo physiological significance of these adrenergic antibodies in a well-phenotyped and representative cohort of patients with POTS and a matched cohort of healthy control subjects, and will characterize the stability of these autoantibodies over time in affected POTS patients.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autonomic and Antibody Assessments | Experimental | Drug: phenylephrine, Drug: isoproterenol, Radiation: 25 micro-Ci of radiation, Procedure: Posture study with blood samples, Procedure: 24-hour heart rhythm and blood pressure monitoring, Procedure: Quantitative Axonal Sudomotor Reflex Testing, Procedure: Autonomic function tests, Other: Rebreathing test, Other: Assessment of splanchnic capacitance, Procedure: microneurographyOn up to 3 study days, POTS patients and control subjects will have several tests to assess autonomic function and to detect the presence of autoantibodies to adrenergic receptors. The following tests will de done but in some participants it may not be necessary to do all of them. The investigator will discuss with each participant which particular tests will be done in each particular case: * Posture study with blood samples for autoantibody testing * 24-hour heart rhythm and blood pressure monitoring * autonomic function tests * Quantitative Axonal Sudomotor Reflex Testing * Total blood volume assessment * Pharmacologic testing with phenylephrine * Pharmacologic testing with isoproterenol * Cardiac output with rebreathing * Assessment of splanchnic capacitance * Microneurography |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 18-50 years old
- Postural Tachycardia Syndrome: Heart rate increase >30 bpm from supine within 10 min of standing, in the absence of orthostatic hypotension (>20/10 mmHg fall in blood pressure), with chronic symptoms (> 6 months), and in the absence of other acute cause of orthostatic tachycardia.
- Able and willing to provide informed consent
- Female premenopausal subjects must utilize adequate birth control and willingness to undergo serum beta-hCG testing
- The subject must understand and be able to comply with the study procedures and restrictions.
Key exclusion criteria (14 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 stand)
- Pregnancy
- Cardiovascular disease, such as myocardial infarction within 6 months, angina pectoris, significant arrhythmia (sinus tachycardia is not excluded), deep vein thrombosis, pulmonary embolism
- History of serious neurologic disease
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 |
|---|---|---|
| phenylephrinePhenylephrine is a selective α1-adrenergic receptor agonist. It will be given in IV bolus injections starting from 12.5 ug. Incremental doses will be given every ~3 min up to 800 ug or until systolic blood pressure increases by 25 mmHg | Drug | Autonomic and Antibody Assessments |
| isoproterenolAlso: isuprel, isoprenalineIsoproterenol is non-selective beta-adrenergic agonist. It will be given in IV bolus injections starting from 0.025 ug. Incremental doses will be given every ~3 min until heart rate increases by 25 bpm. This intervention is optional. | Drug | Autonomic and Antibody Assessments |
| 25 micro-Ci of radiationAlso: DAXORUsing injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation, blood samples are drawn before and 30 minutes after injection. | Radiation | Autonomic and Antibody Assessments |
| Posture study with blood samplesAlso: orthostatic challenge, orthostatic stress testBlood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes. Blood will be drawn in each position to measure hormones that regulate blood pressure and blood volume. An additional sample will be collected in the supine position for the autoantibody assessment. | Procedure or surgery | Autonomic and Antibody Assessments |
| 24-hour heart rhythm and blood pressure monitoringAlso: 24 HolterBlood pressure, heart rate and ECG monitoring for 24 hours | Procedure or surgery | Autonomic and Antibody Assessments |
| Quantitative Axonal Sudomotor Reflex TestingAlso: QSART, sweat testThe QSART assesses the ability of sympathetic nerve terminals in the skin to release acetylcholine and increase sweat production. The test is performed at 4 sites over the forearm, proximal lateral leg, medial distal leg and proximal foot. | Procedure or surgery | Autonomic and Antibody Assessments |
| Autonomic function testsThe autonomic function tests will determine how well the autonomic nervous system regulates blood pressure and heart rate. These tests include breathing deeply for two minutes, breathing fast for 30 seconds, maintaining a handgrip for 3 minutes, breathing against pressure for 15 seconds, and placing the hand in ice water for 1 minute. In addition, participants will be tilted up on a tilt table for up to 10 minutes while recording their heart rate, blood pressure and cardiac output. | Procedure or surgery | Autonomic and Antibody Assessments |
| Rebreathing testAlso: cardiac output measurementCardiac output will be measured using the rebreathing technique (Innocor) | Other | Autonomic and Antibody Assessments |
| Assessment of splanchnic capacitanceSplanchnic capacitance will be assessed using cpap and body impedance to construct pressure volume curves | Other | Autonomic and Antibody Assessments |
| microneurographyAlso: msnamicroneurography will be measured in the peroneal nerve to assess sympathetic activity. | Procedure or surgery | Autonomic and Antibody Assessments |
Primary outcome
Autoantibody levels
Time frame: up to 10 minutes
Blood samples collected while supine during the posture study will be analyzed for autoantibody positivity in POTS patients and control subjects.
Blood pressure after phenylephrine boluses
Time frame: 1-2 minutes after bolus injections
Heart rate after isoproterenol boluses
Time frame: 1-2 minutes after bolus injections
Orthostatic change in heart rate
Time frame: up to 10 minutes
Difference between standing and supine heart rates.
2 secondary outcomes
Blood pressure response during phase IV of the Valsalva maneuver
Time frame: up to 10 minutes
Hear rate response during phase IV of the Valsalva maneuver
Time frame: up to 10 minutes
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 12 Nov 2025.
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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.
Luis Okamoto, MD principal investigator
Vanderbilt University Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing phenylephrine, isoproterenol and 25 micro-Ci of radiation in people with Postural Orthostatic Tachycardia Syndrome and Postural Tachycardia Syndrome, run by Vanderbilt University Medical Center at 2 sites 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 5 inclusion and 14 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: enrolling by invitation, as of the sponsor's last update on 12 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
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?
Autoantibody levels (time frame: up to 10 minutes). The study lists 4 primary outcomes in all. 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 12 Nov 2025.