Postural Tachycardia SyndromePOTSNCT04137757
fMRI in Postural Tachycardia Syndrome
A study testing Lower Body Negative Pressure in people with Postural Tachycardia Syndrome, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Postural Tachycardia Syndrome
- What is being tested?
- Lower Body Negative Pressure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Feb 2022to 1 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: 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.
Read the 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.
- Conditions
- Postural Tachycardia Syndrome
- Being tested
- Lower Body Negative Pressure, Sham Pressure
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lower Body Negative PressureOther
Lower body negative pressure will be applied.
Sham PressureOther
Noise will be turned on but no pressure will be applied.
| Study group | Role | What they receive |
|---|---|---|
| Lower Body Negative Pressure (LBNP) | Experimental | Participants complete mental tasks and imaging while undergoing lower body negative pressure (LBNP). Receives: Other: Lower Body Negative Pressure |
| Sham Pressure | Sham comparator | Participants complete mental tasks and imaging with pressure noise but no pressure. Receives: Other: Sham Pressure |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 60 minutes
Secondary outcomes (4)
Brain Oxygen Perfusion
The change in brain oxygen perfusion measured by arterial spin labeling magnetic resonance imaging following cognitive tasks and orthostatic stress.
Measured: 60 minutes
Blood Pressure
The change in blood pressure following cognitive tasks and orthostatic stress.
Measured: 60 minutes
Heart Rate
The change in heart rate following cognitive tasks and orthostatic stress.
Measured: 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.
Measured: 10 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2019
- Study start18 Feb 2022
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postural Tachycardia SyndromeStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Principal investigator, Amy Arnold, Milton S. Hershey Medical Center
- Investigators
- Amy Arnold, Ph.D., Principal investigator, Pennsylvania State University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04137757
- Sponsor's protocol ID
- Study00012860
- Other IDs
- UL1TR002014
- Acronym
- POTS
- Status last verified
- Sep 2026
- First submitted
- 22 Oct 2019
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Correlates of Cognitive Dysfunction in Postural Tachycardia Syndrome
- ClinicalTrials.gov ID
- NCT04137757
- Acronym / sponsor ID
- POTS / Study00012860
- Conditions
- Postural Tachycardia Syndrome
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Study start
- 18 Feb 2022 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 24 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lower Body Negative Pressure (LBNP) | Experimental | Other: Lower Body Negative PressureParticipants complete mental tasks and imaging while undergoing lower body negative pressure (LBNP). |
| Sham Pressure | Sham comparator | Other: Sham PressureParticipants complete mental tasks and imaging with pressure noise but no pressure. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- Age <18 years or >60 years
- Pregnant or breastfeeding women
- Left handedness
- Require glasses for vision correction (contact lenses are okay)
- Current smokers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lower Body Negative PressureLower body negative pressure will be applied. | Other | Lower Body Negative Pressure (LBNP) |
| Sham PressureNoise will be turned on but no pressure will be applied. | Other | Sham Pressure |
Primary outcome
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.
4 secondary outcomes
Brain Oxygen Perfusion
Time frame: 60 minutes
Blood Pressure
Time frame: 60 minutes
Heart Rate
Time frame: 60 minutes
Stroop Word-Color Score
Time frame: 10 minutes
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Arnold, Ph.D. principal investigator
Pennsylvania State University College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lower Body Negative Pressure in people with Postural Tachycardia Syndrome, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Brain Region Activation (time frame: 60 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.