Vagal Stimulation in POTS

March 16, 2023 updated by: Italo Biaggioni, Vanderbilt University Medical Center

Vagal Stimulation in POTS - The Autonomic Inflammatory Reflex (Pilot 3)

The purpose of this study is to investigate how the electrical stimulation of a nerve in the skin of the earlobe (transcutaneous vagal nerve stimulation), alone or in combination with two medications (galantamine and pyridostigmine), affects the way the autonomic (involuntary) nervous system controls heart rhythm, symptoms on standing, and inflammatory markers in female patients with postural tachycardia syndrome (POTS). The study consists of 2 parts: a screening (1-2 study days), and 3 testing days. The study will take 5 days total and about 16 participants will be screened for the study. The investigators estimate 13 will be eligible to participate in all of the study days.

Study Overview

Detailed Description

This study 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 excessive increase in heart rate, standing tolerance and inflammation in patients with POTS. For this purpose, the investigators will use electrical stimulation of a nerve in the skin of the earlobe (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.

Screening Procedures: Potential participants will be screened in the Vanderbilt Autonomic Dysfunction Center (ADC). Medications affecting heart rate, blood pressure, blood volume, inflammatory markers and the autonomic nervous system will be withdrawn for at least five half-lives before studies. Patients will undergo a complete history and physical examination, ECG, routine clinical laboratory analyses and a blood pregnancy test for women of childbearing potential. Autonomic testing including a posture study with plasma catecholamines is then performed to determine if they meet the inclusion/exclusion criteria.

Eligible participants will be studied on three separate days in a randomized, double-blind, crossover fashion. On each testing day, patients will be given one dose of the study medication (either pyridostigmine, galantamine or placebo pill), and then will have two tilt table tests (a motorized table with a footboard that moves to an upright position): one with the vagal stimulation and one with sham electrical stimulation. Heart rhythm, blood pressure and the amount of fluid in the body (body impedance) will be monitored during studies. Blood samples (up to a total of 2 tablespoons per study day) will also be collected. The order of the study days and tilt tests will be decided at random, like the toss of a coin. Each study day will last about 5 hours.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Autonomic Dysfunction Center/ Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female subjects of 18-45 years, with Postural Tachycardia Syndrome (POTS) as defined by a heart rate increase ≥30 bpm from supine within 10 min of standing or head-up tilt in the absence of orthostatic hypotension, with chronic symptoms (> 6 months), and in the absence of other acute cause of orthostatic tachycardia.
  • Subjects able and willing to provide informed consent

Exclusion Criteria:

  • Pregnancy.
  • Medical conditions that can explain postural tachycardia (e.g., dehydration, medications).
  • Patients who are bedridden or chair-ridden
  • Subjects taking any medication known to affect autonomic function or inflammatory markers (e.g. corticosteroids) who could not discontinue them before study participation.
  • Conditions 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.
  • Other factors which in the investigator's opinion would prevent the subject from completing the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo pill with vagal/sham stimulation
Patients will receive a single oral dose of placebo sugar pill, and 1.5-2 hours later they will have two tilt table tests: one with vagal stimulation and one with sham vagal stimulation
placebo single oral dose
Other Names:
  • placebo
Vagal stimulation will be given at 50 Hz during the tilt table tests
Other Names:
  • Transcutaneous vagal nerve stimulation
Sham vagal stimulation will be given at 0.01 mA during the tilt table tests
Experimental: Pyridostigmine with vagal/sham stimulation
Patients will receive a single oral dose of pyridostigmine pill 30 mg, and 1.5-2 hours later they will have two tilt table tests: one with vagal stimulation and one with sham vagal stimulation
Vagal stimulation will be given at 50 Hz during the tilt table tests
Other Names:
  • Transcutaneous vagal nerve stimulation
Sham vagal stimulation will be given at 0.01 mA during the tilt table tests
pyridostigmine bromide 30 mg single oral dose
Other Names:
  • Mestinon
  • pyridostigmine bromide
Experimental: Galantamine with vagal/sham stimulation
Patients will receive a single oral dose of galantamine pill 8 mg, and 1.5-2 hours later they will have two tilt table tests:one with vagal stimulation and one with sham vagal stimulation
Vagal stimulation will be given at 50 Hz during the tilt table tests
Other Names:
  • Transcutaneous vagal nerve stimulation
Sham vagal stimulation will be given at 0.01 mA during the tilt table tests
Galantamine hydrobromide 8mg single oral dose
Other Names:
  • Razadyne
  • Galantamine hydrobromide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
High frequency variability of heart rate
Time Frame: Up to 15 min of head up tilt
Average of high frequency variability of heart rate during the head up tilt
Up to 15 min of head up tilt

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2017

Primary Completion (Anticipated)

June 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

April 18, 2017

First Submitted That Met QC Criteria

April 18, 2017

First Posted (Actual)

April 21, 2017

Study Record Updates

Last Update Posted (Actual)

March 17, 2023

Last Update Submitted That Met QC Criteria

March 16, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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