Clinical trial NCT03124355: Vagal Stimulation in POTS
Official title: Vagal Stimulation in POTS - The Autonomic Inflammatory Reflex (Pilot 3)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Postural Tachycardia Syndrome
Keywords: vagal stimulation
POTS
galantamine
pyridostigmine
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2017-04-21
Enrollment: 11
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, double-blind, crossover
Primary purpose: BASIC_SCIENCE

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affecting heart rate, blood pressure, blood volume, inflammatory markers and the autonomic nervous system will be withdrawn for at least five half-lives before studies.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

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.

Primary outcomes:
measure: High frequency variability of heart rate
timeFrame: Up to 15 min of head up tilt
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Autonomic Dysfunction Center/ Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Italo Biaggioni, MD
role: PRINCIPAL_INVESTIGATOR
References: