Autoimmune Basis for Postural Tachycardia Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that an antibody-mediated autoimmune reaction will cause symptoms of autonomic dysfunction in some patients with postural tachycardia syndrome (POTS). The investigators further hypothesize that electrical stimulation of the vagus nerve will improve POTS symptoms, autoimmunity and inflammation.

Detailed Description
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The present study is designed to test the hypothesis that muscarinic autoantibody-mediated parasympathetic dysfunction contributes to the pathogenesis of POTS, and that parasympathetic (vagal) stimulation improves POTS symptoms, autoimmunity and inflammation. Define and determine the prevalence, burden, and clinical significance of muscarinic autoantibodies in a well-phenotyped cohort of POTS patients with and without gastroparesis and a matched cohort of healthy control subjects. Evaluate the impact of vagal stimulation on antibody suppression, inflammatory inhibition, and symptom improvement in POTS patients. Non-invasive transcutaneous stimulation of the auricular branch of the vagus nerve (tragus stimulation) will be used to increase parasympathetic activity.

Official Title
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Autoimmune Basis for Postural Tachycardia Syndrome

Conditions
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Postural Tachycardia Syndrome

Intervention / Treatment
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* Device: Vagal stimulation
* Device: Sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-80 years old, female or male Either healthy control or individual with postural tachycardia syndrome (POTS) defined as 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 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 of standing) Cardiovascular disease, such as myocardial infarction within 6 months History or presence of significant immunological or hematological disorders History of vagotomy Currently pregnant women or women planning on becoming pregnant ≤ 3 months Inability to comply with the protocol Patients with active implants (such as a cardiac pacemaker, or a cochlear implant) 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vagal stimulation<br>Vagal stimulation will be given at 20 Hz for 1 hour daily with the bipolar electrode attached to the tragus for 2 months. | Device: Vagal stimulation<br>* Vagal stimulation<br>* Other names: Transcutaneous electrical nerve stimulation;|
| Sham Comparator: Sham stimulation<br>Sham stimulation will be given at 20 Hz for 1 hour daily with the bipolar electrode attached to the earlobe for 2 months. | Device: Sham stimulation<br>* Sham vagal stimulation<br>* Other names: Transcutaneous electrical nerve stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate variability | Average of heart rate variability during the posture test | 5 minute | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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POTS, Vagal Stimulation, Autoantibody