fMRI in Postural Tachycardia Syndrome (POTS)

September 18, 2025 updated by: Amy Arnold, Milton S. Hershey Medical Center

Neural Correlates of Cognitive Dysfunction in Postural Tachycardia Syndrome

Postural tachycardia syndrome (POTS) is one of the most common forms of chronic orthostatic intolerance in the United States. This is a disabling disorder characterized by an excessive increase in heart rate upon standing that is accompanied by symptoms such as dizziness and fatigue. One of the most under appreciated and bothersome symptoms of POTS is impaired cognition or "brain fog," which occurs to a level that interferes with daily activities such as work and education. Despite this high impact, the reasons why POTS patients have problems with cognition are not well understood. This project will test the overall hypothesis that "brain fog" in POTS is related to increased activation of cognitive brain regions during mental tasks when compared with healthy subjects, and that this activation is exacerbated by in the presence of orthostatic stress.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

A randomized, double blind, crossover study will be conducted to determine if there are differences in resting brain structure and blood oxygen perfusion in postural tachycardia syndrome (POTS) compared with healthy subjects, and to identify the pattern of brain activation produced by cognitive testing under resting conditions and in the presence of a physical challenge mimicking orthostatic stress (lower body negative pressure, LBNP). This is an outpatient study that requires a screening visit in the Clinical Research Center within the Penn State Hershey Medical Center, and if eligible, two study visits in the Penn State Center for Nuclear Magnetic Resonance Imaging involving blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) and a cognitive test while lying in a magnetic resonance imaging (MRI) scanner with the lower body placed in the LBNP chamber. The LBNP chamber applies suction to the lower body to pool blood in the legs and physiologically mimic what happens when standing up. Blood pressure, heart rate, and oxygen saturation will be measured throughout the study. A scan will be performed while at rest to look at the structure and blood oxygen perfusion in the brain. The LBNP or sham pressure will then be initiated, with the order determined randomly and the other stress applied at the second study visit. Once the appropriate level of pressure is achieved, brain oxygen perfusion will be measured and subjects will be asked to complete one test of cognitive function. At the end of the cognitive test, brain oxygen levels will be measured and the testing will end. The time inside the MRI scanner at each study visit will be approximately 45 minutes.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 56 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Men and women of all races or ethnicity
  • Age 18-60
  • Healthy volunteers or previously diagnosed with POTS by current consensus criteria (rise in heart rate of at least 30 beats/minute within 10 minutes of standing; absence of orthostatic hypotension defined as a drop in blood pressure greater than 20/10 mmHg within 3 minutes of standing; and presence of daily orthostatic symptoms for at least 6 months such as lightheadedness, dizziness, nausea, and palpitations).
  • Healthy participants must have cognitive testing scores within normal range (defined by Stroop word-color test score between 40-70) and be able to tolerate lower body negative pressure.
  • POTS participants must have either mild cognitive dysfunction (defined by Stroop word-color t-score <40 and >30) or normal cognitive function (defined by Stroop word-color test score between 40-70), and able to tolerate lower body negative pressure.
  • Capable of giving informed consent
  • Fluent in written and spoken English

Exclusion Criteria:

  • Age <18 years or >60 years
  • Pregnant or breastfeeding women
  • Left handedness
  • Require glasses for vision correction (contact lenses are okay)
  • Current smokers
  • Alcohol or drug abuse
  • Recreational drug use (e.g. cannabis, heroin, cocaine)
  • Other potential causes for tachycardia (e.g. prolonged bed rest, dehydration)
  • Taking selective norepinephrine reuptake inhibitors or stimulant medications within the past 3 months as these may alter cognition
  • Unable to tolerate an MRI scanner (e.g. claustrophobia, implanted metal)
  • Unable to give or withdraw informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lower Body Negative Pressure (LBNP)
Participants complete mental tasks and imaging while undergoing lower body negative pressure (LBNP).
Other: Lower Body Negative Pressure
Lower body negative pressure will be applied.
Sham Comparator: Sham Pressure
Participants complete mental tasks and imaging with pressure noise but no pressure.
Other: Sham Pressure
Noise will be turned on but no pressure will be applied.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cognitive Brain Region Activation
Time Frame: 60 minutes
The change in activation of cognitive brain regions measured by blood oxygen dependent functional magnetic resonance imaging following cognitive tasks and orthostatic stress.
60 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Brain Oxygen Perfusion
Time Frame: 60 minutes
The change in brain oxygen perfusion measured by arterial spin labeling magnetic resonance imaging following cognitive tasks and orthostatic stress.
60 minutes
Blood Pressure
Time Frame: 60 minutes
The change in blood pressure following cognitive tasks and orthostatic stress.
60 minutes
Heart Rate
Time Frame: 60 minutes
The change in heart rate following cognitive tasks and orthostatic stress.
60 minutes
Stroop Word-Color Score
Time Frame: 10 minutes
The change in the Stroop word-color test score following orthostatic stress and sham stress. This test measure executive function. The scores are T-scores normalized to population averages based on age and education level from 0 to 100. A higher score indicates better executive function.
10 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Milton S. Hershey Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Center for Advancing Translational Sciences (NCATS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Amy Arnold, Ph.D., Pennsylvania State University College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 18, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 22, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 24, 2019

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 19, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Study00012860
  • UL1TR002014 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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