Vagal Stimulation in POTS

NCT03124355 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 6111
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Postural Tachycardia Syndrome

Keywords

vagal stimulation; POTS; galantamine; pyridostigmine

Outcome Measures

Primary Outcomes (1)

• High frequency variability of heart rate

  Average of high frequency variability of heart rate during the head up tilt

  Up to 15 min of head up tilt

Study Arms (3)

Placebo pill with vagal/sham stimulation

EXPERIMENTAL

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; Device: Vagal stimulation; Device: Sham vagal stimulation

Pyridostigmine with vagal/sham stimulation

EXPERIMENTAL

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; Device: Vagal stimulation; Device: Sham vagal stimulation

Galantamine with vagal/sham stimulation

EXPERIMENTAL

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; Device: Vagal stimulation; Device: Sham vagal stimulation

Interventions

placebo sugar pill DRUG

placebo single oral dose

Also known as: placebo

Placebo pill with vagal/sham stimulation

Pyridostigmine Pill DRUG

pyridostigmine bromide 30 mg single oral dose

Also known as: pyridostigmine bromide, Mestinon

Pyridostigmine with vagal/sham stimulation

Galantamine Pill DRUG

Galantamine hydrobromide 8mg single oral dose

Also known as: Galantamine hydrobromide, Razadyne

Galantamine with vagal/sham stimulation

Vagal stimulation DEVICE

Vagal stimulation will be given at 50 Hz during the tilt table tests

Also known as: Transcutaneous vagal nerve stimulation

Galantamine with vagal/sham stimulation; Placebo pill with vagal/sham stimulation; Pyridostigmine with vagal/sham stimulation

Sham vagal stimulation DEVICE

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

Galantamine with vagal/sham stimulation; Placebo pill with vagal/sham stimulation; Pyridostigmine with vagal/sham stimulation

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Autonomic Dysfunction Center/ Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Interventions

Pyridostigmine Bromide; Galantamine; Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amaryllidaceae Alkaloids; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Electric Stimulation Therapy; Therapeutics

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators will be blinded to the study drugs (placebo, galantamine, pyridostigmine). Participants will be blinded to the vagal stimulation (stimulation vs. sham).
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Model Details: Randomized, double-blind, crossover

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: April 21, 2017
• Study Start: September 30, 2017
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)