Phenotyping of Postural Orthostatic Tachycardia Syndrome (POTS)

Multimodality Deep Phenotyping of Postural Orthostatic Tachycardia Syndrome (POTS), Aim 1

This is an observational study to deeply phenotype the disorder of POTS using multiple testing modalities.

Study Overview

• Status: Recruiting
• Conditions: Postural Orthostatic Tachycardia Syndrome
• Intervention / Treatment: Diagnostic test: multimodal diagnostic testing

Detailed Description

This comprehensive multimodality deep phenotyping will improve the diagnostic approach, inform the development of new treatments, and allow the targeting of therapies to specific POTS patients. The investigators will further identify the diagnostic tools, biomarkers, and clinical outcome measures most relevant to defining the disorder in clinical practice.

The specific aim is to (1) Define clinical POTS classifications from multimodal clinical and laboratory data, (2) address exercise tolerance in POTS using metabolomic assessments, (3) evaluate novel POTS-specific patient outcome measures and (4) evaluate one year outcome data for POTS

Specific research tests will include blood work (for immunophenotyping and neurohormonal assessments), autonomic function testing, skin biopsy (to evaluate intraepidermal nerve fiber density), CO (Carbon Monoxide) rebreathing (for quantitative measurement of plasma volume and red blood cell mass), patient surveys (to characterize symptom profile and disease impact). Blood biosamples will be stored as a repository for future research questions.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Steve Hopkins; Phone Number: 214-648-9275; Email: steve.hopkins@utsouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75208
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Steven Hopkins; Phone Number: 214-648-9275; Email: steve.hopkins@utsouthwestern.edu
      • Contact: Steven Hopkins; Phone Number: 2146489275; Email: steve.hopkins@utsouthwestern.edu
      • Principal Investigator: Steven Vernino, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

POTS patients and Normal Control

Description

Inclusion Criteria:

POTS Patients

• Age ≥ 14 years, able to provide informed consent (assent with parental consent for age < 18) and comply with procedures
• Meets consensus criteria for POTS: (1) sustained increase in heart rate ≥ 30 bpm above supine baseline within 10 min of quiet standing or upright tilt (≥ 40 bpm in individuals 12 to 19 years of age) OR sustained upright HR (heart rate) >120 bpm, (2) absence of orthostatic hypotension, (3) symptoms with standing that improve with sitting or lying down, (4) resting supine heart rate < 100 bpm, (5) orthostatic symptoms present for at least 6 months
• Stable oral medication regimen for at least 14 days

Non-POTS Control Patients

• Healthy women, age 18 - 30 years, able to provide informed consent and comply with study procedures
• Does NOT meet consensus criteria for postural tachycardia syndrome
• No symptoms of orthostatic intolerance or dysautonomia. No history of other major medical disorder
• Resting supine heart rate < 100 bpm

Exclusion Criteria:

None of the following exclusion criteria:

• Use of amphetamine-type stimulants, diuretics, selective norepinephrine reuptake inhibitor, anticholinergic medications (including tricyclic antidepressant medications), fludrocortisone, desmopressin in past 14 days
• Use of other autonomic drugs (adrenergic agents, pyridostigmine, droxidopa, triptans, ivabradine) in past 48 hours
• Currently receiving IVIG (Intravenous immunoglobulin), subcutaneous IgG (Immunoglobulin G), or any investigational medication (in past year)
• Infusion of iv fluids in past 7 days
• History or evidence of another condition explaining symptoms or orthostatic tachycardia (e.g. structural heart disease, CSF (Cerebrospinal fluid) hypovolemia, or severe traumatic brain injury)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
POTS; Patients meeting clinical criteria for postural orthostatic tachycardia syndrome who meet other criteria for inclusion.	Diagnostic test: multimodal diagnostic testing; Serological testing, cardiac MRI, skin biopsy, cardiovascular testing, blood volume measurements
Healthy matched controls; Age and sex matched controls	Diagnostic test: multimodal diagnostic testing; Serological testing, cardiac MRI, skin biopsy, cardiovascular testing, blood volume measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotyping POTS	Assignment of participant to a phenotypic group(s) based on analysis of multimodal data	2 weeks
Natural history	Patient reported functional and subjective change. Surveys including COMPASS31 (Composite Autonomic Symptom Score-31) on a score of 0-100.	1 year
Natural history	patient-reported global impression of outcome on a scale of	1 year

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Steven Vernino, MD PhD, UT Southwestern Medical Center

Publications and helpful links

General Publications

• Raj SR, Bourne KM, Stiles LE, Miglis MG, Cortez MM, Miller AJ, Freeman R, Biaggioni I, Rowe PC, Sheldon RS, Shibao CA, Diedrich A, Systrom DM, Cook GA, Doherty TA, Abdallah HI, Grubb BP, Fedorowski A, Stewart JM, Arnold AC, Pace LA, Axelsson J, Boris JR, Moak JP, Goodman BP, Chemali KR, Chung TH, Goldstein DS, Darbari A, Vernino S. Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2. Auton Neurosci. 2021 Nov;235:102836. doi: 10.1016/j.autneu.2021.102836. Epub 2021 Jun 30.
• Bryarly M, Phillips LT, Fu Q, Vernino S, Levine BD. Postural Orthostatic Tachycardia Syndrome: JACC Focus Seminar. J Am Coll Cardiol. 2019 Mar 19;73(10):1207-1228. doi: 10.1016/j.jacc.2018.11.059.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• 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: STU-2023-0589; 1R01HL166272-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No