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Trial record 17 of 61 for:    Postural Tachycardia Syndrome

Autoimmune Basis for Postural Tachycardia Syndrome

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ClinicalTrials.gov Identifier: NCT02725060
Recruitment Status : Recruiting
First Posted : March 31, 2016
Last Update Posted : January 25, 2018
Sponsor:
Collaborator:
University of Oklahoma
Information provided by (Responsible Party):
Luis E Okamoto, Vanderbilt University Medical Center

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.

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

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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

Arm Intervention/treatment
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:

  • 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
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.
Other Names:
  • isuprel
  • isoprenaline

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.
Other Names:
  • orthostatic challenge
  • orthostatic stress test

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.
Other Names:
  • QSART
  • sweat test

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

Procedure: microneurography
microneurography will be measured in the peroneal nerve to assess sympathetic activity.
Other Name: msna




Primary Outcome Measures :
  1. 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.

  2. Blood pressure after phenylephrine boluses [ Time Frame: 1-2 minutes after bolus injections ]
  3. Heart rate after isoproterenol boluses [ Time Frame: 1-2 minutes after bolus injections ]
  4. Orthostatic change in heart rate [ Time Frame: up to 10 minutes ]
    Difference between standing and supine heart rates.


Secondary Outcome Measures :
  1. Blood pressure response during phase IV of the Valsalva maneuver [ Time Frame: up to 10 minutes ]
  2. Hear rate response during phase IV of the Valsalva maneuver [ Time Frame: up to 10 minutes ]


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.


Information from the National Library of Medicine

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


Contacts
Contact: Bonnie Black, RN 615-322-3304 adcresearch@vanderbilt.edu
Contact: Luis E Okamoto, MD 615-936-6119 adcresearch@vanderbilt.edu

Locations
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    adcresearch@vanderbilt.edu   
Contact: Luis E Okamoto, MD    615-936-6119    adcresearch@vanderbilt.edu   
Sub-Investigator: Bonnie K Black, RN         
Sub-Investigator: Luis E Okamoto, MD         
Principal Investigator: David Robertson, MD         
Sponsors and Collaborators
Vanderbilt University Medical Center
University of Oklahoma
Investigators
Principal Investigator: Luis Okamoto, MD Vanderbilt University Medical Center

Responsible Party: Luis E Okamoto, Research Instructor, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT02725060     History of Changes
Other Study ID Numbers: 151791
First Posted: March 31, 2016    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018

Keywords provided by Luis E Okamoto, Vanderbilt University Medical Center:
POTS
Orthostatic Intolerance
Orthostatic Tachycardia

Additional relevant MeSH terms:
Syndrome
Tachycardia
Postural Orthostatic Tachycardia Syndrome
Cardiovascular Diseases
Nervous System Diseases
Arrhythmias, Cardiac
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Disease
Pathologic Processes
Heart Diseases
Neurologic Manifestations
Signs and Symptoms
Phenylephrine
Isoproterenol
Oxymetazoline
Autoantibodies
Cardiotonic Agents
Mydriatics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sympathomimetics
Vasoconstrictor Agents
Nasal Decongestants
Respiratory System Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists