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

21 Participants Needed

Trial Summary

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 data supports the effectiveness of this treatment for POTS?

The research suggests that patients with POTS experience reduced cerebral blood flow and cognitive difficulties, which are linked to their symptoms. While the studies do not directly address the effectiveness of the treatments listed, they highlight the importance of understanding cerebral blood flow in managing POTS symptoms. ^{1 2 3 4 5}

Is fMRI safe for humans?

Functional Magnetic Resonance Imaging (fMRI) is generally considered safe for humans as it is a non-invasive imaging technique that does not use ionizing radiation. However, individuals with certain metal implants or devices should consult with their doctor before undergoing an fMRI. ^{1 3 5 6 7}

How is the fMRI treatment for POTS different from other treatments?

fMRI (functional magnetic resonance imaging) is unique because it is a non-invasive imaging tool that maps brain activity by detecting changes in blood flow, rather than directly treating symptoms. This approach is different from typical treatments for POTS (Postural Orthostatic Tachycardia Syndrome), which often involve medications or lifestyle changes to manage symptoms. ^{8 9 10 11 12}

What is the purpose of this trial?

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.

Research Team

Amy Arnold, Ph.D.

Principal Investigator

Pennsylvania State University College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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) 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Cerebral Blood Flow and Cognitive Performance in Postural Tachycardia Syndrome: Insights from Sustained Cognitive Stress Test. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Cognitive and psychological issues in postural tachycardia syndrome. [2020]

3. Japan pubmed.ncbi.nlm.nih.gov

Brain fog in postural tachycardia syndrome: An objective cerebral blood flow and neurocognitive analysis. [2022]

4. Switzerland 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. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Oscillatory cerebral blood flow is associated with impaired neurocognition and functional hyperemia in postural tachycardia syndrome during graded tilt. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Postural orthostatic tachycardia syndrome (POTS). [2021]

7. England pubmed.ncbi.nlm.nih.gov

Cognitive dysfunction in postural tachycardia syndrome. [2021]

8. India pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging of the brain: a quick review. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging in pediatrics. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical applications and future directions of functional MRI. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

Presurgical functional magnetic resonance imaging in patients with brain tumors. [2015]