Vagal Nerve Stimulation for POTS

Overseen By Xichun Yu

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

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)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether stimulating the vagus nerve can help individuals with postural tachycardia syndrome (POTS), a condition where standing causes the heart to race. Researchers believe some POTS symptoms may be linked to an immune reaction, and vagus nerve stimulation could reduce these symptoms and related inflammation. Participants will receive either actual vagal nerve stimulation or a sham (fake) version to compare effects. Individuals who have had POTS for more than six months and experience a rapid heartbeat without blood pressure drops when standing might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for POTS.

Will I have to stop taking my current medications?

The trial protocol does not specify if participants with POTS need to stop their current medications. However, healthy control subjects must not be on any chronic medications during the study.

What prior data suggests that vagal nerve stimulation is safe for POTS patients?

Research has shown that vagal nerve stimulation is generally well-tolerated by people with postural orthostatic tachycardia syndrome (POTS). Some studies indicate that this treatment can help reduce the rapid heart rate increase that occurs when standing, a common POTS symptom.

Regarding safety, previous patients have found this therapy safe, experiencing only minor side effects. These may include skin irritation where the device contacts the skin or mild discomfort during the session. Serious side effects are rare.

Overall, vagal nerve stimulation appears to be a promising and safe option for managing POTS symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about vagal nerve stimulation for treating Postural Orthostatic Tachycardia Syndrome (POTS) because it offers a non-drug approach that targets the body's nervous system directly. Unlike standard treatments like beta-blockers or fludrocortisone, which focus on managing symptoms through medication, vagal stimulation uses a small device attached to the tragus (part of the ear) to send electrical impulses, potentially improving autonomic nervous system function. This method could provide a new avenue for managing POTS symptoms by directly modulating nerve signals, offering hope for those who may not find relief with traditional drug therapies.

What evidence suggests that vagal nerve stimulation might be an effective treatment for POTS?

Research has shown that stimulating the vagus nerve (VNS) might help people with postural orthostatic tachycardia syndrome (POTS). Early studies suggest that VNS can slow the rapid heartbeat that occurs when people with POTS stand up. In this trial, participants will receive either Vagal stimulation or Sham stimulation. Some short-term trials found VNS more effective in reducing symptoms than a placebo. Animal studies also showed promise for VNS in managing POTS symptoms. While more research is needed, these findings suggest VNS could be a helpful treatment option for POTS. ^{1 2 3 5 6}

Who Is on the Research Team?

Stavros Stavrakis, MD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with Postural Tachycardia Syndrome (POTS), characterized by a rapid heartbeat upon standing, without other causes of orthostatic tachycardia. Healthy controls must be non-smoking and not on chronic medications. Excluded are those with recent heart attacks, significant immune or blood disorders, pregnancy, pacemakers or cochlear implants, severe hypertension, history of vagotomy.

Inclusion Criteria

I understand and can follow the study's procedures and rules.

I either do not have health issues or have POTS with specific heart rate and blood pressure changes.

Able and willing to provide informed consent

Exclusion Criteria

Patients with active implants (such as a cardiac pacemaker, or a cochlear implant)

My blood pressure is higher than 150/100 mmHg.

I am currently pregnant or planning to become pregnant within the next 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active vagal stimulation or sham stimulation for 2 months

8 weeks

Daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sham stimulation
• Vagal stimulation

Trial Overview

The study aims to see if stimulating the vagus nerve can improve symptoms in POTS patients by potentially reducing autoimmune reactions and inflammation. Participants will receive either actual vagal stimulation or sham (fake) stimulation to compare effects.

How Is the Trial Designed?

Group I: Vagal stimulation Active Control 1 Intervention

Vagal stimulation will be given at 20 Hz for 1 hour daily with the bipolar electrode attached to the tragus for 2 months.

Group II: Sham stimulation Placebo Group 1 Intervention

Sham stimulation will be given at 20 Hz for 1 hour daily with the bipolar electrode attached to the earlobe for 2 months.

Vagal stimulation is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Vagus nerve stimulation for:

• Epilepsy
• Depression
• Cluster headaches

Approved in United States as Vagus nerve stimulation for:

• Epilepsy
• Treatment-resistant depression
• Stroke rehabilitation

Approved in United Kingdom as Vagus nerve stimulation for:

• Epilepsy
• Depression
• Cluster headaches

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 6 patients with drug-resistant epilepsy over 4 years, vagus nerve stimulation (VNS) led to an overall 60% reduction in seizure frequency, with one patient becoming seizure-free, indicating its potential efficacy as a treatment.

The effectiveness of VNS appeared to improve over the first 3 years, with optimal outcomes associated with stimulation currents of 1.5-2.0 mA, suggesting that careful adjustment of stimulation parameters can enhance treatment results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation (VNS) in the treatment of drug-resistant epilepsy. A 4-year follow-up evaluation of VNS treatment efficacy]. Koszewski, W., Bacia, T., Rysz, A.[2015]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

In a study of 24 children undergoing intermittent vagal nerve stimulation over a total of 61 patient years, 15 adverse events were reported, with 13 likely related to the device, indicating a need for careful monitoring during treatment.

Despite the occurrence of adverse events, vagal nerve stimulation was generally well tolerated, and unlike standard drug therapies, these events did not typically require stopping the treatment, although they sometimes led to unexpected surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in children receiving intermittent left vagal nerve stimulation. Murphy, JV., Hornig, GW., Schallert, GS., et al.[2019]

In a study of 61 patients with intractable epilepsy, the output current of vagus nerve stimulation (VNS) did not correlate with the percentage reduction in seizure frequency, indicating that higher current levels are not necessarily more effective.

Interestingly, about 20% of patients who initially did not respond to VNS experienced significant seizure reductions when the output current was increased, suggesting that adjusting current levels may benefit some non-responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for epilepsy: is output current correlated with acute response? Bunch, S., DeGiorgio, CM., Krahl, S., et al.[2007]

A prediction model for the efficacy of vagus nerve stimulation (VNS) in children with drug-resistant epilepsy (DRE) was developed using clinical and EEG synchronization features from 88 children, achieving an accuracy of 75.7% in a discovery cohort.

The model identified significant differences in brain activity patterns, specifically higher interictal awake phase lag index (PLI) in responders compared to non-responders, suggesting that these features can help predict which children are likely to benefit from VNS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prediction model integrating synchronization biomarkers and clinical features to identify responders to vagus nerve stimulation among pediatric patients with drug-resistant epilepsy. Ma, J., Wang, Z., Cheng, T., et al.[2022]

The study identified a specific electrophysiological response called the larynx compound action potential (LCMAP) that occurs approximately 3 ms after vagus nerve stimulation (VNS), which can serve as an objective indicator of effective nerve activation.

LCMAP was successfully recorded in 11 out of 21 rats immediately after surgery, while others required a recovery period, suggesting that monitoring LCMAP could help determine the optimal timing for increasing VNS therapy in patients with refractory epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated assessment of larynx compound muscle action potentials using a self-sizing cuff electrode around the vagus nerve in experimental rats. El Tahry, R., Mollet, L., Raedt, R., et al.[2011]

In a study of 48 patients with intractable partial epilepsy, vagus nerve stimulation (VNS) demonstrated a significant reduction in seizure frequency, with a 26% decrease after 1 year, 30% after 5 years, and 52% after 12 years of treatment.

The side effects of VNS were generally mild to moderate, indicating that it is a safe and tolerable option for patients with difficult-to-treat epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of vagus nerve stimulation in epilepsy patients: a 12-year observation. Uthman, BM., Reichl, AM., Dean, JC., et al.[2019]

In a study of 14 epilepsy patients with vagal nerve stimulators, those who experienced a 50% or greater reduction in seizures (responders) had lower preoperative connections between the left hippocampus and both the left and right thalamus compared to non-responders, suggesting these connections may help predict treatment outcomes.

The study found that varying the stimulation current (up to 1.5 mA) and duration (up to 3 months) did not significantly alter hippocampal-thalamic connectivity, indicating that these parameters may not be critical for immediate changes in brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of vagal nerve stimulation on hippocampal-thalamic functional connectivity in epilepsy patients. Zhu, J., Xu, C., Zhang, X., et al.[2021]

In a retrospective study of 62 patients treated with vagus nerve stimulation (VNS) for epilepsy, only 6 patients experienced significant seizure reduction, indicating that while VNS can be beneficial, it may not be effective for the majority of patients.

Contrary to its reputation for low adverse effects, the study found that only 9 patients had no adverse effects, with some experiencing severe and even life-threatening complications, highlighting the need for careful monitoring throughout the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation therapy in epilepsy patients: long-term outcome and adverse effects: a retrospective analysis]. Carius, A., Wintermantel, A.[2022]

In a study of 138 patients with refractory epilepsy, vagus nerve stimulation (VNS) led to a significant average reduction of 51% in monthly seizure frequency over a mean follow-up of 44 months, demonstrating its efficacy as an adjunctive treatment.

The responder rate, defined as patients experiencing at least a 50% reduction in seizures, was 59%, with 9% of patients achieving complete seizure freedom, indicating that VNS can provide substantial benefits for many patients with difficult-to-treat epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. De Herdt, V., Boon, P., Ceulemans, B., et al.[2007]

Vagal nerve stimulation (VNS) is considered a safe alternative therapy for epilepsy, although it can have rare but significant complications.

The study highlights cases of four patients who were implanted with VNS without prior video-EEG monitoring, suggesting a need for better guidelines on the necessity of this monitoring before VNS implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Video EEG monitoring prior to vagal nerve stimulator implantation. Attarian, H., Dowling, J., Carter, J., et al.[2019]

In a review of 111 patients who received vagus nerve stimulation (VNS) for refractory epilepsy, three cases of intraoperative bradycardia were observed during device testing, but no adverse cardiac events occurred postoperatively.

Despite the initial bradycardia during testing, all three patients experienced reduced seizure frequency after starting VNS therapy, indicating that VNS is safe and effective for managing epilepsy even when bradycardia is noted during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. Ardesch, JJ., Buschman, HP., van der Burgh, PH., et al.[2022]

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Postural orthostatic tachycardia (POTS) is characterized by abnormalities in the autonomic nervous system in the body. The autonomic nervous system controls and ...

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sciencedirect.com/science/article/abs/pii/S0953620525004078

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VNS is a safe and effective adjunctive treatment for drug-resistant epilepsy when surgery is inadvisable. In VNS therapy, the left vagal nerve is stimulated at ...

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Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS).