Neuromodulation for Heart Failure

(TREAT-HF Trial)

Overseen By Tarun Dasari, MD,MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

Disqualifiers: Congenital heart disease, Vagotomy, AV block, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3-6 days

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment that stimulates a part of the ear to help calm the body's stress responses and reduce inflammation in patients with severe heart failure. The goal is to see if this can improve their heart function and overall health.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for heart failure?

Research shows that low-level tragus stimulation (LLTS) can improve heart function by enhancing heart rate variability and reducing strain on the heart muscle. It has also shown promise in improving heart conditions like atrial fibrillation and heart failure with preserved ejection fraction. ^{1 2 3 4 5}

Is low-level tragus stimulation safe for humans?

Low-level tragus stimulation (LLTS) has been studied in humans for various conditions, including heart failure and epilepsy, and is generally considered safe. Studies have shown it can be used without significant discomfort or adverse effects, as it is a non-invasive method that stimulates the vagus nerve through the skin. ^{1 2 3 4 5}

How is tragus stimulation treatment different from other heart failure treatments?

Tragus stimulation is a unique, non-invasive treatment that uses low-level electrical impulses to stimulate the vagus nerve through the ear, which can help improve heart function by balancing the nervous system's control over the heart. Unlike traditional heart failure treatments that often involve medications or invasive procedures, this approach targets the body's natural nerve pathways to potentially reduce heart strain and improve heart health. ^{1 2 3 5 6}

Research Team

Tarun Dasari, M.D.

Principal Investigator

OUHSC

Eligibility Criteria

This trial is for patients admitted with Acute Decompensated Heart Failure (ADHF). It's not suitable for those who refuse consent, have complex heart conditions like Tetralogy of Fallot, history of frequent fainting due to low heart rate or blood pressure, major nerve surgery in the neck, severe heartbeat irregularities, are pregnant or imprisoned, and those with advanced kidney disease or certain infections like Hepatitis C or HIV.

Inclusion Criteria

I was admitted to the hospital for acute decompensated heart failure.

Exclusion Criteria

I have had surgery to cut the nerves to my stomach.

I have Hepatitis C or HIV.

You have a specific type of heart block called 2nd or 3rd degree AV block.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive either active or sham tragus stimulation for 2 hours daily

3-6 days

Daily visits during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tragus Stimulation

Trial Overview The study tests if Low Level Tragus Stimulation (LLTS), a non-invasive technique that affects nerve activity related to the heart can reduce inflammation markers in the blood and improve symptoms such as difficulty breathing. Participants will be randomly assigned to receive either real LLTS or a sham treatment daily during their hospital stay.

Participant Groups

Group I: Tragus Stimulation Experimental Treatment 1 Intervention

In this group patients will receive neuromodulation for 2 hours daily

Group II: Control group Active Control 1 Intervention

Sham neuromodulation will be done

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Findings from Research

Low-level tragus stimulation (LLTS) is a promising non-invasive treatment that has shown potential benefits in managing various cardiovascular conditions, including atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF).

Preliminary clinical studies suggest that LLTS may improve heart function and reduce arrhythmias by positively influencing the balance between the sympathetic and parasympathetic nervous systems, although further research and larger trials are needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive Low-level Tragus Stimulation in Cardiovascular Diseases. Jiang, Y., Po, SS., Amil, F., et al.[2020]

In a study involving 24 patients with diastolic dysfunction, low-level transcutaneous vagus nerve stimulation (LLTS) significantly improved left ventricular function, as indicated by a 1.8% increase in global longitudinal strain compared to sham stimulation.

LLTS also positively affected heart rate variability, suggesting it enhances autonomic tone, which may contribute to better cardiac mechanics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans. Tran, N., Asad, Z., Elkholey, K., et al.[2020]

Chronic intermittent low-level tragus stimulation (LL-TS) significantly reduced left atrial and left ventricular dilatation and improved heart function in dogs with healed myocardial infarction, demonstrating its efficacy in cardiac remodeling.

After 90 days of treatment, LL-TS also decreased cardiac fibrosis and reduced levels of inflammatory and fibrotic markers in the heart, suggesting a mechanism of action that involves reducing inflammation and fibrosis post-infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic intermittent low-level transcutaneous electrical stimulation of auricular branch of vagus nerve improves left ventricular remodeling in conscious dogs with healed myocardial infarction. Wang, Z., Yu, L., Wang, S., et al.[2014]

In a study involving 10 patients undergoing coronary artery bypass grafting, low-level vagus nerve stimulation through the tragus (tLLVNS) significantly increased unipolar potential voltage, indicating enhanced atrial electrophysiological properties.

Some patients experienced additional benefits during tLLVNS, such as reduced total activation time and changes in sinoatrial node exit sites, suggesting potential antiarrhythmic effects that could help in preventing atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights Into the Effects of Low-Level Vagus Nerve Stimulation on Atrial Electrophysiology: Towards Patient-Tailored Cardiac Neuromodulation. Kharbanda, RK., Ramdat Misier, NL., van Schie, MS., et al.[2023]

In a study involving 26 patients with ischemic cardiomyopathy and heart failure, acute low-level tragus stimulation (LLTS) was found to significantly increase the T-wave alternans (TWA) burden during sinus rhythm, indicating a potential risk for ventricular tachy-arrhythmias.

The study demonstrated that the increase in TWA burden was heart-rate dependent, particularly during right atrial pacing at 100 bpm, suggesting that LLTS may not have the desired anti-arrhythmic effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure. Kulkarni, K., Stavrakis, S., Elkholey, K., et al.[2021]

In a study involving 28 adult beagle dogs, low-level tragus nerve stimulation (LL-TS) significantly improved heart function and reduced left ventricular dilation after myocardial infarction, suggesting its potential as a therapeutic intervention.

The mechanism behind this improvement appears to involve increased activity in atrial ganglion plex and changes in specific proteins (α7nAChR and MMP-9), indicating that LL-TS may help in cardiac remodeling through neural pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive tragus stimulation improves cardiac post-ischemic remodeling by regulating cardiac parasympathetic activity. Chen, M., Chen, H., Wang, Z., et al.[2023]

References

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

Non-invasive Low-level Tragus Stimulation in Cardiovascular Diseases. [2020]

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

Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans. [2020]

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

Chronic intermittent low-level transcutaneous electrical stimulation of auricular branch of vagus nerve improves left ventricular remodeling in conscious dogs with healed myocardial infarction. [2014]

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

Insights Into the Effects of Low-Level Vagus Nerve Stimulation on Atrial Electrophysiology: Towards Patient-Tailored Cardiac Neuromodulation. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure. [2021]

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

Non-invasive tragus stimulation improves cardiac post-ischemic remodeling by regulating cardiac parasympathetic activity. [2023]