NCT02725060

Autoimmune Basis for Postural Tachycardia Syndrome

• Status: Enrolling By Invitation
• Phase: N/A
• Study type: Interventional
• Enrollment: 58 (estimated)
• Sponsor: Vanderbilt University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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.

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
• Cardiovascular Diseases
• Primary Dysautonomias

Interventions

Type	Name	Description
DRUG	phenylephrine	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
DRUG	isoproterenol	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.
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
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	Assessment of splanchnic capacitance	Splanchnic capacitance will be assessed using cpap and body impedance to construct pressure volume curves
PROCEDURE	microneurography	microneurography will be measured in the peroneal nerve to assess sympathetic activity.

Timeline

• Start date: 2016-02-01
• Primary completion: 2026-10-01
• Completion: 2026-12-01
• First posted: 2016-03-31
• Last updated: 2025-11-12

Locations

2 sites across 1 country: United States