Vagal Stimulation in POTS

Postural Tachycardia Syndrome Clinical Trial

Official title:

Vagal Stimulation in POTS - The Autonomic Inflammatory Reflex (Pilot 3)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03124355
• Other study ID #: 6111
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 30, 2017
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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affecting heart rate, blood pressure, blood volume, inflammatory markers and the autonomic nervous system will be withdrawn for at least five half-lives before studies.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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Postural Orthostatic Tachycardia Syndrome
• Postural Tachycardia Syndrome
• Tachycardia

Intervention

Drug:
• placebo sugar pill
placebo single oral dose
• Pyridostigmine Pill
pyridostigmine bromide 30 mg single oral dose
• Galantamine Pill
Galantamine hydrobromide 8mg single oral dose

Device:
• Vagal stimulation
Vagal stimulation will be given at 50 Hz during the tilt table tests
• Sham vagal stimulation
Sham vagal stimulation will be given at 0.01 mA during the tilt table tests

Locations

Country	Name	City	State
United States	Autonomic Dysfunction Center/ Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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