Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 45 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Randomized, double-blind, crossover
Primary Purpose
Basic Science
Masking
Double (Participant, Investigator)
Masking Description
Participants and investigators will be blinded to the study drugs (placebo, galantamine, pyridostigmine). Participants will be blinded to the vagal stimulation (stimulation vs. sham).

Arm Groups

ArmDescriptionAssigned Intervention
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
  • Drug: placebo sugar pill
    placebo single oral dose
    Other names:
    • placebo
  • Device: Vagal stimulation
    Vagal stimulation will be given at 50 Hz during the tilt table tests
    Other names:
    • Transcutaneous vagal nerve stimulation
  • Device: Sham vagal 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
  • Drug: Pyridostigmine Pill
    pyridostigmine bromide 30 mg single oral dose
    Other names:
    • pyridostigmine bromide
    • Mestinon
  • Device: Vagal stimulation
    Vagal stimulation will be given at 50 Hz during the tilt table tests
    Other names:
    • Transcutaneous vagal nerve stimulation
  • Device: Sham vagal stimulation
    Sham vagal stimulation will be given at 0.01 mA during the tilt table tests
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
  • Drug: Galantamine Pill
    Galantamine hydrobromide 8mg single oral dose
    Other names:
    • Galantamine hydrobromide
    • Razadyne
  • Device: Vagal stimulation
    Vagal stimulation will be given at 50 Hz during the tilt table tests
    Other names:
    • Transcutaneous vagal nerve stimulation
  • Device: Sham vagal stimulation
    Sham vagal stimulation will be given at 0.01 mA during the tilt table tests

Recruiting Locations

Autonomic Dysfunction Center/ Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
Emily C Smith, RN
615-875-1516
autonomics@vumc.org

More Details

NCT ID
NCT03124355
Status
Recruiting
Sponsor
Vanderbilt University Medical Center

Study Contact

Emily C Smith, RN
615.875.1516
autonomics@vumc.org

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.