Autoimmune Basis for Postural Tachycardia Syndrome

Cardiovascular Diseases Clinical Trial

Official title:

Autoimmune Basis for Postural Tachycardia Syndrome

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02725060
• Other study ID #: 151791
• Status: Enrolling by invitation
• Phase: N/A
• Start date: February 2016
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 58
• Est. completion date: December 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• phenylephrine
Phenylephrine is a selective a1-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
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.
• 24-hour heart rhythm and blood pressure monitoring
Blood pressure, heart rate and ECG monitoring for 24 hours
• 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.
• 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)
• 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.

Locations

Country	Name	City	State
United States	Autonomic Dysfunction Center	Nashville	Tennessee
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	University of Oklahoma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Blood pressure after phenylephrine boluses		1-2 minutes after bolus injections
Primary	Heart rate after isoproterenol boluses		1-2 minutes after bolus injections
Primary	Orthostatic change in heart rate	Difference between standing and supine heart rates.	up to 10 minutes
Secondary	Blood pressure response during phase IV of the Valsalva maneuver		up to 10 minutes
Secondary	Hear rate response during phase IV of the Valsalva maneuver		up to 10 minutes