Vagal Stimulation in POTS

NCT ID: NCT03124355

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-30
• Study Completion Date: 2026-12-31

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.

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affecting heart rate, blood pressure, blood volume, inflammatory markers and the autonomic nervous system will be withdrawn for at least five half-lives before studies.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

Conditions

Postural Tachycardia Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Galantamine Pill

Intervention Type: DRUG

Galantamine hydrobromide 8mg single oral dose

Vagal stimulation

Intervention Type: DEVICE

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

Sham vagal stimulation

Intervention Type: DEVICE

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

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

Group Type: EXPERIMENTAL

placebo sugar pill

Intervention Type: DRUG

placebo single oral dose

Vagal stimulation

Intervention Type: DEVICE

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

Sham vagal stimulation

Intervention Type: DEVICE

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

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

Group Type: EXPERIMENTAL

Pyridostigmine Pill

Intervention Type: DRUG

pyridostigmine bromide 30 mg single oral dose

Vagal stimulation

Intervention Type: DEVICE

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

Sham vagal stimulation

Intervention Type: DEVICE

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

Interventions

placebo sugar pill

placebo single oral dose

Intervention Type: DRUG

Pyridostigmine Pill

pyridostigmine bromide 30 mg single oral dose

Intervention Type: DRUG

Galantamine Pill

Galantamine hydrobromide 8mg single oral dose

Intervention Type: DRUG

Vagal stimulation

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

Intervention Type: DEVICE

Sham vagal stimulation

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

Intervention Type: DEVICE

Other Intervention Names

placebo; pyridostigmine bromide; Mestinon; Galantamine hydrobromide; Razadyne; Transcutaneous vagal nerve stimulation

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Italo Biaggioni

Professor of Medicine and Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Italo Biaggioni, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Autonomic Dysfunction Center/ Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

6111

Identifier Type: -

Identifier Source: org_study_id