6111: Vagal Stimulation in POTS – The Autonomic Inflammatory Reflex (Pilot 3)

Status: Recruiting

Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.

Study Summary

The purpose of this study is to investigate how the electrical stimulation of a nerve in the skin of your ear lobe (transcutaneous vagal nerve stimulation) affects the way your autonomic (involuntary) nervous system controls your heart rhythm.

For Diseases:

  • Postural Tachycardia Syndrome (POTS)

Background

Postural tachycardia syndrome (POTS) is a chronic condition characterized by disabling intolerance to upright posture associated with increased heart rate, symptoms while standing, and increased levels of inflammatory markers. Previous studies have found that patients with POTS have also a dramatic decrease in the activity of part of the autonomic (involuntary) nervous system called the parasympathetic nervous system. In this study, we will test the hypothesis that impairment of the parasympathetic nervous system contributes to the symptoms of POTS, and that stimulation of this part of the nervous system improves the exaggerated increase in heart rate, standing tolerance and inflammation in patients with POTS. For this purpose, we will use electrical stimulation of a nerve in the skin of your ear lobe (transcutaneous vagal nerve stimulation) and two medications that increase the levels of acetylcholine (a neurotransmitter) in the central or peripheral nervous system (galantamine and pyridostigmine, respectively) to increase the activity of the parasympathetic nervous system.

The research objectives are:

  1. To compare the effects of transcutaneous vagal nerve stimulation with that of sham electrical stimulation, galantamine and pyridostigmine on the electrical activity of the heart, symptoms while standing and inflammatory markers.
  2. To compare the effect of the combination of transcutaneous vagal nerve stimulation and pyridostigmine/galantamine with that of each intervention alone.

This is a randomized, double-blind, crossover pilot study. About 16 participants will be screened for the study. We estimate that 13 patients will complete the study. Female subjects ages 18 – 45 years of age with Postural Tachycardia Syndrome (POTS) may be able to participate. Eligible subjects will be asked to stop taking any medication that may interfere with our testing for up to seven days prior to the study days. This study will be conducted at Vanderbilt University Medical Center. This study consists of 2 parts: a screening (1-2 study days), and 3 testing days. The study will take 5 days total.

During the screening days, you may be asked to:

  • Answer questions and complete questionnaires about your health, medical history and family health history. We may look at your medical records so that we can collect information about your medical history.
  • Have a Medical Exam
  • Have your blood taken for routine labs and pregnancy test.
  • Provide a urine sample
  • Have an electrocardiogram (test that measures the electrical activity of your heart)
  • Have standard autonomic testing.
  • Participate in a tilt table test (a motorized table with a footboard that moves you to an upright position without you having to use your muscles to stand)

On each testing day, you will be given one dose of the study medication (either pyridostigmine, galantamine or placebo pill), and then you will have 2 tilt table tests (a motorized table with a footboard that moves you to an upright position without you having to use your muscles to stand): one with the vagal stimulation and one with sham electrical stimulation. We will measure your heart rhythm with an electrocardiogram, your blood pressure, the amount of fluid in your body (body impedance) and we will draw blood samples (up to a total of 2 tablespoons per study day). The order of the study days and tilt tests will be decided at random, like the toss of a coin. You and the doctors will not know which study medication you are receiving. Each study day will last ~ 5 hours.

Targeted Enrollment

To be eligible to participate, you must:

  • Be a female of 18-45 years old.
  • Have Postural Tachycardia Syndrome (POTS).
  • Able and willing to provide informed consent.

You are not eligible to participate if:

  • Are pregnant.
  • Have any medical condition that can explain postural tachycardia (e.g., dehydration, medications).
  • Are bedridden or chair-ridden.
  • Take any medication known to affect autonomic function or inflammatory markers (e.g. corticosteroids) and could not discontinue them before study participation.
  • Have any condition associated with chronic inflammatory processes which in the investigator’s opinion would affect the interpretation of the results. Examples may include smoking, diabetes, BMI>30 kg/m2, current infections or cancer.

Stay Connected - Join the Contact Regsitry

The RDCRN Autonomic Disorders Consortium Contact Registry is a way for patients with rare diseases and their family members to learn about research studies they may be able to join.

Learn More

In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation

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