Autoimmune Basis for Postural Tachycardia Syndrome

The purpose of this study is to test the hypothesis that an antibody-mediated autoimmune reaction will cause symptoms of autonomic dysfunction in some patients with postural tachycardia syndrome (POTS). The investigators further hypothesize that electrical stimulation of the vagus nerve will improve POTS symptoms, autoimmunity and inflammation.

Study Overview

• Status: Recruiting
• Conditions: Postural Tachycardia Syndrome
• Intervention / Treatment: Device: Vagal stimulation; Device: Sham stimulation

Detailed Description

The present study is designed to test the hypothesis that muscarinic autoantibody-mediated parasympathetic dysfunction contributes to the pathogenesis of POTS, and that parasympathetic (vagal) stimulation improves POTS symptoms, autoimmunity and inflammation.

Define and determine the prevalence, burden, and clinical significance of muscarinic autoantibodies in a well-phenotyped cohort of POTS patients with and without gastroparesis and a matched cohort of healthy control subjects.

Evaluate the impact of vagal stimulation on antibody suppression, inflammatory inhibition, and symptom improvement in POTS patients. Non-invasive transcutaneous stimulation of the auricular branch of the vagus nerve (tragus stimulation) will be used to increase parasympathetic activity.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xichun Yu; Phone Number: 47779 405-271-5896; Email: xichun-yu@ouhsc.edu
• Study Contact Backup: Name: Brittany Karfonta; Phone Number: 34889 405-271-3480; Email: Brittany-Karfonta@ouhsc.edu

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Oklahoma Clinical and Translational Science Institute
      • Contact: Brittany Karfonta; Phone Number: 405-271-3480; Email: OSCTR@ouhsc.edu
      • Principal Investigator: Stavros Stavrakis, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-80 years old, female or male
• Either healthy control or individual with postural tachycardia syndrome (POTS) defined as heart rate increase >30 bpm from supine within 10 min of standing, in the absence of orthostatic hypotension (>20/10 mmHg fall in blood pressure), with chronic symptoms (>6 months), and in the absence of other acute cause of orthostatic tachycardia
• Able and willing to provide informed consent
• Understand and be able to comply with the study procedures and restrictions

Exclusion Criteria:

• Hypertension (>150 mmHg systolic and >100 mmHg diastolic) based on history or findings at screening
• Orthostatic hypotension (consistent drop in blood pressure >20/10 mmHg with 10 min of standing)
• Cardiovascular disease, such as myocardial infarction within 6 months
• History or presence of significant immunological or hematological disorders
• History of vagotomy
• Currently pregnant women or women planning on becoming pregnant ≤ 3 months
• Inability to comply with the protocol
• Patients with active implants (such as a cardiac pacemaker, or a cochlear implant)

Healthy control subjects will be healthy, non-smoking and on no chronic medications at the time of the study. Healthy control subjects will be group-matched to the POTS patients for age and gender.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vagal stimulation; Vagal stimulation will be given at 20 Hz for 1 hour daily with the bipolar electrode attached to the tragus for 2 months.	Device: Vagal stimulation; Vagal stimulation; Other Names: Transcutaneous electrical nerve stimulation
Sham Comparator: Sham stimulation; Sham stimulation will be given at 20 Hz for 1 hour daily with the bipolar electrode attached to the earlobe for 2 months.	Device: Sham stimulation; Sham vagal stimulation; Other Names: Transcutaneous electrical nerve stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate variability	Average of heart rate variability during the posture test	5 minute

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Director: Stavros Stavrakis, MD, University of Oklahoma

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2022
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: September 8, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: POTS; Autoantibody; Vagal Stimulation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Disease; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Syndrome; Tachycardia; Postural Orthostatic Tachycardia Syndrome
• Other Study ID Numbers: 13705; 2R01HL128393-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No