Clinical trial

Autoimmune Basis for Postural Tachycardia Syndrome

Name
151791
Description
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.
Trial arms
Trial start
2016-02-01
Estimated PCD
2024-10-01
Trial end
2024-12-01
Treatment
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
Arms:
Autonomic and Antibody Assessments
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.
Arms:
Autonomic and Antibody Assessments
Other names:
isuprel, isoprenaline
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.
Arms:
Autonomic and Antibody Assessments
Other names:
DAXOR
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.
Arms:
Autonomic and Antibody Assessments
Other names:
orthostatic challenge, orthostatic stress test
24-hour heart rhythm and blood pressure monitoring
Blood pressure, heart rate and ECG monitoring for 24 hours
Arms:
Autonomic and Antibody Assessments
Other names:
24 Holter
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.
Arms:
Autonomic and Antibody Assessments
Other names:
QSART, sweat test
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.
Arms:
Autonomic and Antibody Assessments
Rebreathing test
Cardiac output will be measured using the rebreathing technique (Innocor)
Arms:
Autonomic and Antibody Assessments
Other names:
cardiac output measurement
Assessment of splanchnic capacitance
Splanchnic capacitance will be assessed using cpap and body impedance to construct pressure volume curves
Arms:
Autonomic and Antibody Assessments
microneurography
microneurography will be measured in the peroneal nerve to assess sympathetic activity.
Arms:
Autonomic and Antibody Assessments
Other names:
msna
Size
58
Primary endpoint
Autoantibody levels
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
up to 10 minutes
Eligibility criteria
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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 58, 'type': 'ESTIMATED'}}
Updated at
2024-03-26

1 organization

2 products

8 indications

Indication
Tachycardia
Indication
Arrhythmia
Indication
Cardiac