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Autoimmune Basis for Postural Tachycardia Syndrome

Primary Purpose

Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, Tachycardia

Status
Enrolling by invitation
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
phenylephrine
isoproterenol
25 micro-Ci of radiation
Posture study with blood samples
24-hour heart rhythm and blood pressure monitoring
Quantitative Axonal Sudomotor Reflex Testing
Autonomic function tests
Rebreathing test
Assessment of splanchnic capacitance
microneurography
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Postural Orthostatic Tachycardia Syndrome focused on measuring POTS, Orthostatic Intolerance, Orthostatic Tachycardia

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of Oklahoma Health Sciences Center
  • Autonomic Dysfunction Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autonomic and Antibody Assessments

Arm Description

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

Outcomes

Primary Outcome Measures

Autoantibody levels
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
Heart rate after isoproterenol boluses
Orthostatic change in heart rate
Difference between standing and supine heart rates.

Secondary Outcome Measures

Blood pressure response during phase IV of the Valsalva maneuver
Hear rate response during phase IV of the Valsalva maneuver

Full Information

First Posted
February 22, 2016
Last Updated
May 21, 2023
Sponsor
Vanderbilt University Medical Center
Collaborators
University of Oklahoma
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1. Study Identification

Unique Protocol Identification Number
NCT02725060
Brief Title
Autoimmune Basis for Postural Tachycardia Syndrome
Official Title
Autoimmune Basis for Postural Tachycardia Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
February 2016 (undefined)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
University of Oklahoma

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, Tachycardia, Arrhythmias, Cardiac, Autonomic Nervous System Diseases, Orthostatic Intolerance, Cardiovascular Diseases, Primary Dysautonomias
Keywords
POTS, Orthostatic Intolerance, Orthostatic Tachycardia

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Autonomic and Antibody Assessments
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
phenylephrine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
isoproterenol
Other Intervention Name(s)
isuprel, isoprenaline
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
25 micro-Ci of radiation
Other Intervention Name(s)
DAXOR
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Posture study with blood samples
Other Intervention Name(s)
orthostatic challenge, orthostatic stress test
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
24-hour heart rhythm and blood pressure monitoring
Other Intervention Name(s)
24 Holter
Intervention Description
Blood pressure, heart rate and ECG monitoring for 24 hours
Intervention Type
Procedure
Intervention Name(s)
Quantitative Axonal Sudomotor Reflex Testing
Other Intervention Name(s)
QSART, sweat test
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Autonomic function tests
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Rebreathing test
Other Intervention Name(s)
cardiac output measurement
Intervention Description
Cardiac output will be measured using the rebreathing technique (Innocor)
Intervention Type
Other
Intervention Name(s)
Assessment of splanchnic capacitance
Intervention Description
Splanchnic capacitance will be assessed using cpap and body impedance to construct pressure volume curves
Intervention Type
Procedure
Intervention Name(s)
microneurography
Other Intervention Name(s)
msna
Intervention Description
microneurography will be measured in the peroneal nerve to assess sympathetic activity.
Primary Outcome Measure Information:
Title
Autoantibody levels
Description
Blood samples collected while supine during the posture study will be analyzed for autoantibody positivity in POTS patients and control subjects.
Time Frame
up to 10 minutes
Title
Blood pressure after phenylephrine boluses
Time Frame
1-2 minutes after bolus injections
Title
Heart rate after isoproterenol boluses
Time Frame
1-2 minutes after bolus injections
Title
Orthostatic change in heart rate
Description
Difference between standing and supine heart rates.
Time Frame
up to 10 minutes
Secondary Outcome Measure Information:
Title
Blood pressure response during phase IV of the Valsalva maneuver
Time Frame
up to 10 minutes
Title
Hear rate response during phase IV of the Valsalva maneuver
Time Frame
up to 10 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luis Okamoto, MD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73117-1213
Country
United States
Facility Name
Autonomic Dysfunction Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

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Autoimmune Basis for Postural Tachycardia Syndrome

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