Vagus Nerve Stimulation in Treatment of Postural Orthostatic Tachycardia Syndrome

Study Overview
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Brief Summary
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Postural orthostatic tachycardia (POTS) is characterized by abnormalities in the autonomic nervous system in the body. The autonomic nervous system controls and regulates body functions such as heart rate, breathing, digestion, and more. The investigator has shown that patients with POTS have higher cardiovascular and adrenergic activating autoantibodies (AAb), which likely changes the normal make-up of POTS. There are autoantibodies that have been suggested by a few reports of their presence in POTS, but their role different aspects of POTS is unknown. The study will look at the body's responses in patients with POTS. The crossover study design is to have half of the patients will start with sham followed by active stimulation and half will start by active followed by sham stimulation. It is anticipated that results will provide a potential therapeutic approach based on the understanding of POTS.

Official Title
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Vagus Nerve Stimulation in Treatment of Postural Orthostatic Tachycardia Syndrome

Conditions
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Postural Orthostatic Tachycardia Syndrome

Intervention / Treatment
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* Device: Parasym (TM) Transcutaneous Electrical Nerve Stimulation (TENS) Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Female or male participants age 18-80 Group 1 (20 participants): A physician-based diagnosis of POTS Participants that have a postural pulse rise of >35 for adolescents and >30 for adults with a Blood Pressure (BP) that does not drop >10/5 mmHg will be qualified. These participants may be on salt and fluid loading. Group 2 (10 participants): Previously diagnosed with POTS Patients is on Intravenous immunoglobulin (IVIG) infusion but who have an incomplete symptomatic response Exclusion Criteria: Age < 18 years Sick sinus syndrome, 2nd or 3rd degree Atrioventricular (AV) block, bifascicular block or prolonged 1st degree AV block (PR>300ms). Currently pregnant women or women planning on becoming pregnant ≤ 6 months History of hypotension due to autonomic dysfunction Have a secondary causes of tachycardia (acute anemia or blood loss, drugs, significant cardiomyopathy, diabetes mellitus) Patients with active implants (such as a cardiac pacemaker, or a cochlear implant).

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Active Treatment to Sham<br>Subjects randomized to the sequence Active Treatment/Sham Treatment arm will be instructed to first use the Parasym (TM) TENS device as active treatment for the first phase of the study. Next, they will be instructed to use the Parasym (TM) TENS device as sham treatment for the second phase of the study. | Device: Parasym (TM) Transcutaneous Electrical Nerve Stimulation (TENS) Device<br>* Daily use of Parasym (TM) device on tragus or ear lobe, as assigned treatment arm<br>|
| Other: Sham to Active Treatment<br>Subjects randomized to the sequence Sham Treatment/Active Treatment arm will be instructed to use the Parasym (TM) TENS device as sham treatment for the first phase of the study. Next, they will be instructed to use the Parasym (TM) TENS device as active treatment for the second phase of the study. | Device: Parasym (TM) Transcutaneous Electrical Nerve Stimulation (TENS) Device<br>* Daily use of Parasym (TM) device on tragus or ear lobe, as assigned treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in orthostatic heart rate | We will measure the average change in heart rate between supine and standing using continuous ECG after two and four months of daily vagal nerve stimulation | 2 and 4 months | 
| Long term effects on M2 muscarinic autoantibody levels | The average change in M2 muscarinic autoantibody levels measured from blood specimens obtained after two and four months of daily vagal nerve stimulation. | 2 and 4 months | 
| Long term effects on beta 1-adrenergic autoantibody levels | The average change in beta 1-adrenergic autoantibody levels measured from blood specimens obtained after two and four months of daily vagal nerve stimulation. | 2 and 4 months | 
| Long term effects on alpha 1-adrenergic autoantibody levels | The average change in alpha 1-adrenergic autoantibody levels measured from blood specimens obtained after two and four months of daily vagal nerve stimulation. | 2 and 4 months | 
| Average change in heart rate variability | We will measure the average change in heart rate variability based on 5 minute ECG after two and four months of daily vagal nerve stimulation | 2 and 4 months |