Autoimmune Basis for Postural Tachycardia Syndrome

NCT02725060 | Enrolling By Invitation

• 1 other identifier: 151791
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

Brief 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. The investigators also want to see if the levels of these autoantibodies stay the same over time.

Conditions

Postural Orthostatic Tachycardia Syndrome; Postural Tachycardia Syndrome; Tachycardia; Arrhythmias, Cardiac; Autonomic Nervous System Diseases; Orthostatic Intolerance; Cardiovascular Diseases; Primary Dysautonomias

Keywords

POTS; Orthostatic Intolerance; Orthostatic Tachycardia

Outcome Measures

Primary Outcomes (4)

• Autoantibody levels

  Blood samples collected while supine during the posture study will be analyzed for autoantibody positivity in POTS patients and control subjects.

  up to 10 minutes

• Blood pressure after phenylephrine boluses

  1-2 minutes after bolus injections

• Heart rate after isoproterenol boluses

  1-2 minutes after bolus injections

• Orthostatic change in heart rate

  Difference between standing and supine heart rates.

  up to 10 minutes

Secondary Outcomes (2)

• Blood pressure response during phase IV of the Valsalva maneuver

  up to 10 minutes

• Hear rate response during phase IV of the Valsalva maneuver

  up to 10 minutes

Study Arms (1)

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

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

Interventions

phenylephrine DRUG

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

Autonomic and Antibody Assessments

isoproterenol DRUG

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.

Also known as: isuprel, isoprenaline

Autonomic and Antibody Assessments

25 micro-Ci of radiation RADIATION

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.

Also known as: DAXOR

Autonomic and Antibody Assessments

Posture study with blood samples PROCEDURE

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.

Also known as: orthostatic challenge, orthostatic stress test

Autonomic and Antibody Assessments

24-hour heart rhythm and blood pressure monitoring PROCEDURE

Blood pressure, heart rate and ECG monitoring for 24 hours

Also known as: 24 Holter

Autonomic and Antibody Assessments

Quantitative Axonal Sudomotor Reflex Testing PROCEDURE

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.

Also known as: QSART, sweat test

Autonomic and Antibody Assessments

Autonomic function tests PROCEDURE

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.

Autonomic and Antibody Assessments

Rebreathing test OTHER

Cardiac output will be measured using the rebreathing technique (Innocor)

Also known as: cardiac output measurement

Autonomic and Antibody Assessments

Assessment of splanchnic capacitance OTHER

Splanchnic capacitance will be assessed using cpap and body impedance to construct pressure volume curves

Autonomic and Antibody Assessments

microneurography PROCEDURE

microneurography will be measured in the peroneal nerve to assess sympathetic activity.

Also known as: msna

Autonomic and Antibody Assessments

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• University of Oklahoma: collaborator

Study Sites (2)

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73117-1213, United States

Location

Autonomic Dysfunction Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Tachycardia; Arrhythmias, Cardiac; Autonomic Nervous System Diseases; Orthostatic Intolerance; Cardiovascular Diseases; Primary Dysautonomias

Interventions

Phenylephrine; Isoproterenol; Blood Specimen Collection; Blood Pressure Monitors

Condition Hierarchy (Ancestors)

Nervous System Diseases; Heart Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Sphygmomanometers; Diagnostic Equipment; Equipment and Supplies

Study Officials

• Luis Okamoto, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Instructor

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: March 31, 2016
• Study Start: February 1, 2016
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 12, 2025

Record last verified: 2025-11

Locations

US (2)