Clinical trial NCT02725060: Autoimmune Basis for Postural Tachycardia Syndrome
Official title: Autoimmune Basis for Postural Tachycardia Syndrome
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: 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
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: University of Oklahoma
First posted: 2016-03-31
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Autoantibody levels
timeFrame: up to 10 minutes
measure: Blood pressure after phenylephrine boluses
timeFrame: 1-2 minutes after bolus injections
measure: Heart rate after isoproterenol boluses
timeFrame: 1-2 minutes after bolus injections
measure: Orthostatic change in heart rate
timeFrame: up to 10 minutes
Secondary outcomes:
measure: Blood pressure response during phase IV of the Valsalva maneuver
timeFrame: up to 10 minutes
measure: Hear rate response during phase IV of the Valsalva maneuver
timeFrame: up to 10 minutes
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Nashville
country: United States
facility: Autonomic Dysfunction Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Luis Okamoto, MD
role: PRINCIPAL_INVESTIGATOR
References: