Autoimmune Investigation for POTS

Enrolling by invitation at 1 trial location

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must not be taking: Chronic medications

Disqualifiers: Hypertension, Cardiovascular disease, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if some individuals with postural tachycardia syndrome (POTS) have elevated levels of certain immune proteins that might influence their symptoms. Researchers will monitor heart rhythm and blood pressure over 24 hours, along with other tests, to assess the consistency of these proteins over time. Individuals with POTS, identified by a heart rate increase of over 30 beats per minute when standing without a drop in blood pressure, may be suitable candidates for this study. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance the understanding and treatment of POTS.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that any underlying disease requiring regular medication that could affect the study might exclude you from participating. It's best to discuss your specific medications with the trial coordinators.

What prior data suggests that these assessments and tests are safe for participants?

Research has shown that the treatments in this study, such as isoproterenol and phenylephrine, have been tested for safety in humans. Isoproterenol can cause serious eye irritation and may irritate the lungs. Some people with POTS might react strongly to isoproterenol, experiencing a fast heartbeat at doses that don't affect healthy individuals.

Phenylephrine is often used in POTS studies because it can improve blood flow and stabilize heart rate and blood pressure when standing. It is generally considered safe, but like all medications, it can have side effects that vary from person to person.

The trial's phase is labeled as "Not Applicable," indicating that the treatments are not new drugs but are used to observe participant responses. This suggests these treatments have been used before in humans and are generally well-tolerated. However, individual reactions can vary, so discussing potential risks with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative ways to understand and manage Postural Orthostatic Tachycardia Syndrome (POTS) by focusing on the autonomic nervous system and potential autoantibodies. Unlike standard treatments, which often involve medications like beta-blockers or fludrocortisone to manage symptoms, this trial aims to uncover the underlying mechanisms of POTS by assessing heart rhythm, blood pressure, and autonomic function in-depth. By investigating the presence of autoantibodies and testing splanchnic capacitance, researchers hope to identify new therapeutic targets, offering a more personalized approach to POTS management. This could lead to breakthroughs in treatment strategies, potentially improving outcomes for patients who don't respond well to current options.

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

Research has shown that some people with postural tachycardia syndrome (POTS) react strongly to isoproterenol, a drug that can raise heart rate. One study found that 13 out of 17 patients experienced a higher-than-normal increase in heart rate after taking this drug. This trial will include pharmacologic testing with isoproterenol to assess its effects on heart rate in POTS patients.

Similarly, phenylephrine, another drug under study in this trial, has been found to help POTS patients stand longer and improve blood flow. It works by narrowing blood vessels, which can help maintain steady blood pressure when standing. These findings suggest that both drugs might help manage POTS symptoms. ^{2 6 7 8 9}

Who Is on the Research Team?

Luis E Okamoto, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for people aged 18-50 with Postural Tachycardia Syndrome (POTS), which causes a rapid heartbeat upon standing. Participants must have had symptoms for over 6 months and be able to follow the study's procedures. Pregnant individuals, those with recent heart issues or significant arrhythmias, liver or kidney problems, low hematocrit levels, uncontrolled hypertension, serious neurological diseases, or immune/hematological disorders cannot join.

Inclusion Criteria

My heart rate increases significantly when I stand up, without a drop in blood pressure, and this has been happening for more than 6 months.

The subject must understand and be able to comply with the study procedures and restrictions.

Able and willing to provide informed consent

Exclusion Criteria

Pregnancy

My blood pressure is higher than 150/100 mmHg.

I have not had a heart attack, severe chest pain, serious irregular heartbeat, deep vein thrombosis, or lung blood clots in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Autonomic and Antibody Assessments

Participants undergo various tests to assess autonomic function and detect autoantibodies to adrenergic receptors

Up to 3 study days

Up to 3 visits (in-person)

Follow-up

Participants are monitored for the stability of autoantibody levels over time

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 24-hour heart rhythm and blood pressure monitoring
• Assessment of splanchnic capacitance
• Autonomic function tests
• isoproterenol
• microneurography
• phenylephrine
• Quantitative Axonal Sudomotor Reflex Testing
• Rebreathing test

Trial Overview The study tests if autoantibodies against autonomic nervous system receptors are present in POTS patients and affect their symptoms. It includes various diagnostic tests like microneurography, blood pressure monitoring over 24 hours, posture studies with blood samples involving minimal radiation exposure, and autonomic function assessments.

How Is the Trial Designed?

Group I: Autonomic and Antibody Assessments Experimental Treatment 10 Interventions

On up to 3 study days, POTS patients and control subjects will have several tests to assess autonomic function and to detect the presence of autoantibodies to adrenergic receptors. The following tests will de done but in some participants it may not be necessary to do all of them. The investigator will discuss with each participant which particular tests will be done in each particular case: * Posture study with blood samples for autoantibody testing * 24-hour heart rhythm and blood pressure monitoring * autonomic function tests * Quantitative Axonal Sudomotor Reflex Testing * Total blood volume assessment * Pharmacologic testing with phenylephrine * Pharmacologic testing with isoproterenol * Cardiac output with rebreathing * Assessment of splanchnic capacitance * Microneurography

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

University of Oklahoma

Collaborator

Trials

484

Recruited

95,900+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6113123/

Postural Tachycardia Syndrome – Diagnosis, Physiology, and ... Some hyperadrenergic POTS patients have hypersensitivity to isoproterenol, with marked tachycardia at doses producing no hemodynamic effect in healthy ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1050173825000933

The evidence for treatments for postural orthostatic ... In this systematic review, we evaluate the evidence for different treatments for POTS from 21 randomized clinical trials with 750 patients that took place ...

3. academic.oup.com academic.oup.com/europace/article/19/7/1211/2952372

Antiadrenergic autoimmunity in postural tachycardia syndrome Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02673996

NCT02673996 | POTS Adrenergic Ab (CIHR Aims #1&2) The investigators propose to perform dose response studies for phenylephrine and isoproterenol in POTS patients and control subjects with blood pressure (BP) ...

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. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/15592m.pdf

Safety Data Sheet Eye irritation 2A. H319 Causes serious eye irritation. Specific target organ toxicity (single exposure) 3 H335 May cause respiratory irritation.

7. ahajournals.org ahajournals.org/doi/10.1161/JAHA.119.014084

Hop to It: The First Animal Model of Autoimmune Postural ... The study demonstrated suppression of orthostatic tachycardia in the rabbit model of POTS by blocking the adrenergic autoantibodies from binding ...

8. imgcdn.mckesson.com imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9VALNT_ISUPREL_AMP_ML.pdf

Isuprel (Isoproterenol Hydrochloride Injection, USP) SAFETY DATA SHEET. Product Name: Isuprel (Isoproterenol Hydrochloride Injection, USP). 1. CHEMICAL PRODUCT AND COMPANY IDENTIFICATION.

9. sciencedirect.com sciencedirect.com/science/article/pii/S0735109719302190

Postural Orthostatic Tachycardia Syndrome: JACC Focus ... The HR after the use of nitroglycerin or isoproterenol should never be used to achieve clinical criteria for POTS. ... Though there are no ...