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Vagal Stimulation in POTS

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ClinicalTrials.gov Identifier: NCT03124355
Recruitment Status : Recruiting
First Posted : April 21, 2017
Last Update Posted : February 4, 2019
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University Medical Center

Brief Summary:
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 or disease Intervention/treatment Phase
Postural Tachycardia Syndrome Drug: placebo sugar pill Drug: Pyridostigmine Pill Drug: Galantamine Pill Device: Vagal stimulation Device: Sham vagal stimulation Phase 1

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affecting heart rate, blood pressure, blood volume, inflammatory markers and the autonomic nervous system will be withdrawn for at least five half-lives before studies.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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomized, double-blind, crossover
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).
Primary Purpose: Basic Science
Official Title: Vagal Stimulation in POTS - The Autonomic Inflammatory Reflex (Pilot 3)
Actual Study Start Date : September 30, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


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
Drug: placebo sugar pill
placebo single oral dose
Other Name: placebo

Device: Vagal stimulation
Vagal stimulation will be given at 50 Hz during the tilt table tests
Other Name: 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 Name: 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 Name: Transcutaneous vagal nerve stimulation

Device: Sham vagal stimulation
Sham vagal stimulation will be given at 0.01 mA during the tilt table tests




Primary Outcome Measures :
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03124355


Contacts
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Contact: Emily C Smith, RN 615.875.1516 autonomics@vumc.org
Contact: Luis Okamoto, MD 615-936-6119 autonomics@vumc.org

Locations
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United States, Tennessee
Autonomic Dysfunction Center/ Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Emily C Smith, RN    615-875-1516    autonomics@vumc.org   
Sub-Investigator: Bonnie K Black, RN         
Sub-Investigator: Luis E Okamoto, MD         
Principal Investigator: Italo Biaggioni, MD         
Sub-Investigator: Alfredo Gamboa, MD         
Sub-Investigator: Cyndya A Shibao, MD         
Sub-Investigator: Andre Diedrich, MD, PhD         
Sub-Investigator: jorge Celedonio, MD         
Sub-Investigator: Emily C Smith, Rn         
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Italo Biaggioni, MD Vanderbilt University Medical Center

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Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03124355     History of Changes
Other Study ID Numbers: 6111
First Posted: April 21, 2017    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Italo Biaggioni, Vanderbilt University Medical Center:
vagal stimulation
POTS
galantamine
pyridostigmine
Additional relevant MeSH terms:
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Postural Orthostatic Tachycardia Syndrome
Tachycardia
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Pathologic Processes
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Bromides
Galantamine
Pyridostigmine Bromide
Anticonvulsants
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Nootropic Agents