fMRI Study for POTS

(POTS Trial)

Overseen By Amy Arnold, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Norepinephrine reuptake inhibitors, Stimulants

Disqualifiers: Pregnancy, Smoking, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores why individuals with postural tachycardia syndrome (POTS) often experience brain fog, which complicates everyday tasks. Researchers aim to determine if brain fog results from the brain working harder during mental tasks, particularly when standing. Participants will undergo brain scans using fMRI (functional magnetic resonance imaging) while performing tasks to observe brain reactions under different conditions. The trial seeks individuals diagnosed with POTS who experience symptoms like dizziness or fatigue when standing, as well as healthy individuals willing to participate in cognitive testing. As an unphased trial, this study offers a unique opportunity to enhance understanding of POTS and its effects on cognitive function.

Will I have to stop taking my current medications?

The trial requires that you have not taken selective norepinephrine reuptake inhibitors or stimulant medications in the past 3 months, as these can affect cognition.

What prior data suggests that fMRI and Lower Body Negative Pressure are safe for studying POTS?

Research has shown that lower body negative pressure (LBNP) is generally well-tolerated by people with postural orthostatic tachycardia syndrome (POTS). Studies indicate that LBNP can reduce blood flow to the heart and brain, yet no evidence of serious side effects exists. People with POTS seem to manage these changes without major problems.

LBNP uses a vacuum to pull blood toward the lower body, helping researchers understand how the body reacts to stress, such as standing up quickly.

Overall, while LBNP affects blood flow to the heart and brain, it appears safe for use in studies with POTS patients. Research has not reported any serious side effects so far. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different interventions, like Lower Body Negative Pressure (LBNP) and sham pressure, affect brain function in people with Postural Orthostatic Tachycardia Syndrome (POTS). Unlike standard treatments for POTS, which often involve medication or lifestyle changes to manage symptoms, this study uses functional MRI (fMRI) to understand the brain's response to these interventions. By examining brain activity in real-time, researchers hope to uncover new insights into the neurological aspects of POTS, potentially leading to more targeted and effective treatment strategies in the future.

What evidence suggests that this trial's treatments could be effective for POTS?

Research has shown that lower body negative pressure (LBNP), a treatment in this trial, can alter blood flow in people with POTS. These changes might reduce stress on the heart and blood vessels, potentially alleviating symptoms like dizziness and brain fog. Studies have found that during LBNP, individuals with POTS experience a greater drop in heart and brain blood flow stress compared to healthy individuals. This suggests that LBNP might help manage POTS by reducing these physical stresses. Although more research is needed, these findings are promising for using LBNP to improve thinking and memory issues related to POTS. Participants in this trial will undergo either LBNP or a Sham Pressure treatment to evaluate these effects. ^{1 3 5 6 7}

Who Is on the Research Team?

Amy Arnold, Ph.D.

Principal Investigator

Pennsylvania State University College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 who either have POTS or are healthy volunteers. Participants must not be pregnant, left-handed, need glasses (contacts okay), smoke, abuse substances, or have other tachycardia causes. They should be fluent in English and able to consent.

Inclusion Criteria

I understand the study and can agree to participate.

I am healthy or have been diagnosed with POTS based on heart rate changes and symptoms.

Fluent in written and spoken English

Exclusion Criteria

You use drugs like cannabis, heroin, or cocaine for fun.

You smoke cigarettes right now.

You abuse alcohol or drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Study Visits

Participants undergo BOLD-fMRI and cognitive testing under resting conditions and with orthostatic stress using LBNP

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after study visits

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• fMRI
• Lower Body Negative Pressure
• Sham Pressure

Trial Overview The study examines if 'brain fog' in POTS patients is due to increased brain activity during mental tasks under stress. It uses fMRI scans with two interventions: Lower Body Negative Pressure and a fake (sham) pressure as a control.

How Is the Trial Designed?

Group I: Lower Body Negative Pressure (LBNP) Experimental Treatment 1 Intervention

Participants complete mental tasks and imaging while undergoing lower body negative pressure (LBNP).

Group II: Sham Pressure Placebo Group 1 Intervention

Participants complete mental tasks and imaging with pressure noise but no pressure.

fMRI is already approved in United States, European Union for the following indications:

Approved in United States as Functional Magnetic Resonance Imaging for:

• Diagnostic imaging for various medical conditions, including neurological disorders such as mild TBI

Approved in European Union as Functional Magnetic Resonance Imaging for:

• Diagnostic imaging for various medical conditions, including neurological disorders such as mild TBI

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

Postural orthostatic tachycardia syndrome (POTS) is defined by a significant increase in heart rate upon standing, specifically over 30 beats per minute in adults and over 40 beats per minute in adolescents, without the presence of other conditions that could cause tachycardia.

The recognition of POTS as a distinct clinical condition has improved, allowing for better understanding of its causes, effects, and management strategies, as illustrated by the two case studies presented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postural orthostatic tachycardia syndrome (POTS). Sidhu, B., Obiechina, N., Rattu, N., et al.[2021]

Patients with postural tachycardia syndrome (POTS) show significant deficits in selective attention and cognitive processing speed compared to healthy individuals, as evidenced by neuropsychological tests involving 28 POTS patients and 24 matched controls.

While POTS patients exhibited difficulties in selective attention and executive function, other cognitive areas like memory and verbal fluency remained unaffected, indicating that the cognitive impairments in POTS are specific rather than widespread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive dysfunction in postural tachycardia syndrome. Arnold, AC., Haman, K., Garland, EM., et al.[2021]

In a study of 22 participants with postural tachycardia syndrome (POTS) and 18 healthy controls, those with POTS experienced a significantly greater reduction in cerebral blood flow velocity (CBFv) after a prolonged cognitive stress test, indicating a potential link between cognitive stress and brain fog symptoms.

The POTS group also showed greater declines in psychomotor speed and increased difficulty concentrating after cognitive stress, suggesting that cognitive challenges can exacerbate symptoms even without changes in posture.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral Blood Flow and Cognitive Performance in Postural Tachycardia Syndrome: Insights from Sustained Cognitive Stress Test. Wells, R., Malik, V., Brooks, AG., et al.[2021]

In a study involving 11 patients with postural tachycardia syndrome (POTS) and 8 healthy individuals, cerebral blood flow (CBF) in the posterior cerebral artery was found to be normal in POTS patients, indicating that CBF is not impaired in these individuals.

Despite normal CBF, POTS patients exhibited significant difficulties with short-term memory and attention, suggesting that these cognitive impairments may contribute to the experience of 'brain fog' commonly reported by these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain fog in postural tachycardia syndrome: An objective cerebral blood flow and neurocognitive analysis. Wells, R., Paterson, F., Bacchi, S., et al.[2022]

Functional magnetic resonance imaging (fMRI) allows researchers to non-invasively observe blood flow changes in the brain, which helps map areas responsible for motor, sensory, and cognitive functions, significantly advancing neuroscience research.

Clinically, fMRI is particularly useful in pre-surgical evaluations for epilepsy and in planning neurosurgeries near critical brain areas, although the review also discusses its limitations and practical considerations for effective use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging of the brain: a quick review. Vaghela, V., Kesavadas, C., Thomas, B.[2013]

Functional magnetic resonance imaging (fMRI) detects changes in blood oxygen levels in the brain, allowing researchers to map brain activity during specific tasks or in resting states.

fMRI has become a crucial tool for studying both normal brain function and various brain diseases, highlighting its importance in clinical applications and emerging research directions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications and future directions of functional MRI. Orringer, DA., Vago, DR., Golby, AJ.[2023]

This study found that patients with Postural Orthostatic Tachycardia Syndrome (POTS) exhibit significant differences in cerebral blood flow velocity (CBFV) and cerebrovascular response to carbon dioxide (CO2) compared to healthy individuals, which may help in diagnosing POTS more accurately.

The research utilized tilt table and hyperventilation techniques to assess CBFV and CO2 levels in POTS patients versus healthy groups, revealing that POTS patients have impaired CBFV responses, indicating a potential mechanism for cognitive impairment associated with the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparisons of the Nonlinear Relationship of Cerebral Blood Flow Response and Cerebral Vasomotor Reactivity to Carbon Dioxide under Hyperventilation between Postural Orthostatic Tachycardia Syndrome Patients and Healthy Subjects. Lin, SL., Yeh, SJ., Chen, CK., et al.[2020]

Functional magnetic resonance imaging (fMRI) is a safe and non-invasive method for assessing brain function in children, allowing researchers and clinicians to study brain activity without needing invasive procedures.

The review highlights that fMRI has significant potential for both research and clinical applications in pediatrics, despite some challenges and limitations specific to this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging in pediatrics. Wilke, M., Holland, SK., Myseros, JS., et al.[2018]

In a study of 34 patients, the distance between benign brain tumors and areas of brain activity (measured using fMRI) was found to be a significant predictor of pre- and postoperative neurological motor deficits, with specific odds ratios indicating increased risk as the distance decreased.

The results suggest that a standardized method for measuring this distance could enhance the clinical utility of fMRI in surgical planning, potentially reducing the risk of neurological deficits after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Presurgical functional magnetic resonance imaging in patients with brain tumors. Ravn, S., Holmberg, M., Sørensen, P., et al.[2015]

In patients with postural tachycardia syndrome (POTS), cognitive impairment while upright is linked to reduced cerebral blood flow (CBF) and decreased neurovascular coupling, as shown by significant declines in memory performance during tilt tests.

During incremental tilts, patients with POTS exhibited increased oscillatory CBF velocity and arterial pressure, which correlated with diminished functional hyperemia and cognitive performance, highlighting the impact of altered blood flow dynamics on brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oscillatory cerebral blood flow is associated with impaired neurocognition and functional hyperemia in postural tachycardia syndrome during graded tilt. Stewart, JM., Del Pozzi, AT., Pandey, A., et al.[2018]

POTS patients experience significant cognitive dysfunction, often described as 'brain fog', which can occur even when they are not standing, indicating a need for further research into effective treatments.

Many POTS patients also show symptoms of mild to moderate depression and anxiety, suggesting that psychotherapy could be beneficial in managing both psychological and physiological aspects of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive and psychological issues in postural tachycardia syndrome. Raj, V., Opie, M., Arnold, AC.[2020]

Functional MRI (fMRI) is a safe and noninvasive imaging tool that allows for repeated scans, making it ideal for studying brain activation in patients with neurological and neuropsychiatric disorders over time.

fMRI has shown potential in identifying abnormal brain activity, understanding neuroplasticity, and serving as a predictive biomarker for disease progression, highlighting its utility in both clinical trials and basic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in functional magnetic resonance imaging: technology and clinical applications. Dickerson, BC.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10942852/

Effect of lower body negative pressure on cardiac and ... We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular ...

2. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/abs/10.14814/phy2.15979

Effect of lower body negative pressure on cardiac and ... We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38490814/

Effect of lower body negative pressure on cardiac and ... We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular ...

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.033485

Long‐Term POTS Outcomes Survey: Diagnosis, Therapy ... The LT‐POTS (Long Term POTS Outcomes Survey) included questions about quality of life, symptoms, therapies, education, employment, and social impact of disease.

5. jacc.org jacc.org/doi/10.1016/j.jacc.2018.11.059

Postural Orthostatic Tachycardia Syndrome This review details the most current views on the potential causes, comorbid conditions, proposed subtypes, differential diagnoses, evaluations, and treatment ...

6. journals.physiology.org journals.physiology.org/doi/abs/10.1152/physiol.2024.39.S1.379

The Cardiac and Cerebrovascular Response to Lower ... We tested the hypothesis that, compared to healthy controls (HC) individuals with POTS would have greater decreases in cardiac, and cerebral ...

7. ahajournals.org ahajournals.org/doi/10.1161/CIRCEP.124.013629

Prevalence and Clinical Impact of Postural Orthostatic ... Postural orthostatic tachycardia syndrome is a common cardiovascular dysautonomia following development of long COVID and can be detected in ...