Autoimmune Basis for Postural Tachycardia Syndrome
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02725060|
Recruitment Status : Recruiting
First Posted : March 31, 2016
Last Update Posted : January 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Postural Orthostatic Tachycardia Syndrome Postural Tachycardia Syndrome Tachycardia Arrhythmias, Cardiac Autonomic Nervous System Diseases Orthostatic Intolerance Cardiovascular Diseases Primary Dysautonomias||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||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||95 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Autoimmune Basis for Postural Tachycardia Syndrome|
|Study Start Date :||February 2016|
|Estimated Primary Completion Date :||February 2021|
|Estimated Study Completion Date :||July 2021|
Experimental: Autonomic and Antibody Assessments
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:
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
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.
Radiation: 25 micro-Ci of 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.
Other Name: DAXOR
Procedure: Posture study with blood samples
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.
Procedure: 24-hour heart rhythm and blood pressure monitoring
Blood pressure, heart rate and ECG monitoring for 24 hours
Other Name: 24 Holter
Procedure: Quantitative Axonal Sudomotor Reflex Testing
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.
Procedure: Autonomic function tests
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.
Other: Rebreathing test
Cardiac output will be measured using the rebreathing technique (Innocor)
Other Name: cardiac output measurement
Other: Assessment of splanchnic capacitance
Splanchnic capacitance will be assessed using cpap and body impedance to construct pressure volume curves
microneurography will be measured in the peroneal nerve to assess sympathetic activity.
Other Name: msna
- 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.
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02725060
|Contact: Bonnie Black, RNemail@example.com|
|Contact: Luis E Okamoto, MDfirstname.lastname@example.org|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center||Active, not recruiting|
|Oklahoma City, Oklahoma, United States, 73117-1213|
|United States, Tennessee|
|Autonomic Dysfunction Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Bonnie Black, RN 615-322-3304 email@example.com|
|Contact: Luis E Okamoto, MD 615-936-6119 firstname.lastname@example.org|
|Sub-Investigator: Bonnie K Black, RN|
|Sub-Investigator: Luis E Okamoto, MD|
|Principal Investigator: David Robertson, MD|
|Principal Investigator:||Luis Okamoto, MD||Vanderbilt University Medical Center|