fMRI in Postural Tachycardia Syndrome (POTS)

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: Recruiting
• Conditions: Postural Tachycardia Syndrome
• Intervention / Treatment: Other: Lower Body Negative Pressure; Other: Sham Pressure

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: Interventional
• Enrollment (Estimated): 55
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aimee J Cauffman, RN; Phone Number: 717-531-1617; Email: acauffman@pennstatehealth.psu.edu
• Study Contact Backup: Name: Amy C Arnold, Ph.D.; Phone Number: 717-531-3674; Email: aca17@psu.edu

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State Milton S. Hershey Medical Center
      • Contact: Aimee Cauffman, RN; Phone Number: 717-531-1617; Email: acauffman@pennstatehealth.psu.edu
      • Contact: Amy Arnold, PhD; Phone Number: 717-531-3674; Email: aca17@psu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and women of all races
• 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).
• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Cognitive Brain Region Activation	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

Outcome Measure	Measure Description	Time Frame
Brain Oxygen Perfusion	The change in brain oxygen perfusion measured by arterial spin labeling magnetic resonance imaging following cognitive tasks and orthostatic stress.	60 minutes
Blood Pressure	The change in blood pressure following cognitive tasks and orthostatic stress.	60 minutes
Heart Rate	The change in heart rate following cognitive tasks and orthostatic stress.	60 minutes
Stroop Word-Color Score	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

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Amy C Arnold, Ph.D., Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 22, 2019
• First Submitted That Met QC Criteria: October 22, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 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: Study00012860; UL1TR002014 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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