- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03124355
Vagal Stimulation in POTS
Vagal Stimulation in POTS - The Autonomic Inflammatory Reflex (Pilot 3)
Study Overview
Status
Conditions
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affecting heart rate, blood pressure, blood volume, inflammatory markers and the autonomic nervous system will be withdrawn for at least five half-lives before studies.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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Tennessee
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Nashville, Tennessee, United States, 37232
- Autonomic Dysfunction Center/ Vanderbilt University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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:
Vagal stimulation will be given at 50 Hz during the tilt table tests
Other Names:
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:
Sham vagal stimulation will be given at 0.01 mA during the tilt table tests
pyridostigmine bromide 30 mg single oral dose
Other Names:
|
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:
Sham vagal stimulation will be given at 0.01 mA during the tilt table tests
Galantamine hydrobromide 8mg single oral dose
Other Names:
|
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
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Up to 15 min of head up tilt
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Nervous System Diseases
- Arrhythmias, Cardiac
- Cardiac Conduction System Disease
- Autonomic Nervous System Diseases
- Primary Dysautonomias
- Orthostatic Intolerance
- Tachycardia
- Postural Orthostatic Tachycardia Syndrome
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Cholinergic Agents
- Enzyme Inhibitors
- Anticonvulsants
- Nootropic Agents
- Cholinesterase Inhibitors
- Parasympathomimetics
- Bromides
- Pyridostigmine Bromide
- Galantamine
Other Study ID Numbers
- 6111
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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