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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether low-level tragus nerve stimulation (LLTNS) can reduce inflammation and improve symptoms in patients with acute decompensated heart failure (ADHF). Heart failure often causes inflammation and other health issues, but traditional treatments have not significantly improved these conditions. Participants will receive either real or sham (fake) stimulation for two hours daily to determine if LLTNS aids in reducing inflammation and enhancing heart function. Individuals hospitalized with ADHF might be suitable candidates for this study. As an unphased trial, this study offers patients a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

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 prior data suggests that this neuromodulation technique is safe for heart failure patients?

Research has shown that low-level tragus nerve stimulation (LLTNS) is generally well-tolerated. Studies have found it can help manage heart issues like atrial fibrillation, an irregular heartbeat. LLTNS is non-invasive, meaning it doesn't involve surgery, which reduces the risk of complications.

Side effects are usually mild and may include slight discomfort where the stimulation is applied. The available data reports no serious side effects related to LLTNS, suggesting it could be a safe option for people with acute decompensated heart failure (ADHF). While researchers are studying LLTNS for its effects on inflammation and heart function, its safety in other heart conditions suggests it is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about tragus stimulation for heart failure because it's a non-invasive technique that aims to improve heart function by tapping into the body's own nervous system. Unlike standard treatments like medications or surgeries that directly target the heart or blood vessels, tragus stimulation works by activating the vagus nerve through a simple device placed on the ear. This method could offer a new way to manage heart failure without the side effects associated with more traditional treatments. Plus, it holds promise for improving patient quality of life by providing a potentially safer and more convenient option.

What evidence suggests that tragus stimulation is effective for heart failure?

Research has shown that stimulating the tragus nerve, a part of the ear, at a low level might help with heart failure by reducing inflammation. Inflammation poses a major issue in heart failure, and this technique is believed to lower harmful substances called cytokines. Studies have found that similar nerve stimulation methods can improve heart function and overall well-being. This approach is non-invasive, meaning it doesn't require surgery, and it works by affecting the body's nervous system to reduce inflammation. In this trial, participants in the Tragus Stimulation arm will receive this neuromodulation for 2 hours daily. While the exact effects on sudden heart failure are still under investigation, early results suggest it could benefit heart function and lower inflammation. ^{2 4 5 6 7}

Who Is on the Research Team?

Tarun Dasari, M.D.

Principal Investigator

OUHSC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12231624/

The efficacy of transcutaneous vagus nerve stimulation in ... t-VNS represents a promising therapeutic modality for heart failure, providing advantages such as improved cardiac function, enhanced well-being, reduced ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02898181

Low Level Tragus Stimulation in Acute Decompensated ... Low-level vagus nerve stimulation via stimulation of teh Tragus (LLTS) is a non-invasive way to modulate autonomic tone and thereby inflammation. Vagal nerve ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.030539

Vagus Nerve Stimulation and Inflammation in ... In the setting of heart failure, VNS was found to improve systolic function and reverse cardiac remodeling. In summary, existing experimental ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405500X23002943

Insights Into the Effects of Low-Level Vagus Nerve ... Low-level vagus nerve stimulation through the tragus (tLLVNS) is increasingly acknowledged as a therapeutic strategy to prevent and treat atrial fibrillation.

5. frontiersin.org frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1052471/full

Chronic vagus nerve stimulation in patients with heart failure Based on these encouraging experimental data, vagus nerve stimulation (VNS) has been assessed in patients with HF with a reduced ejection fraction.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7330730/

Non-invasive Low-level Tragus Stimulation in Cardiovascular ... LLTS has shown promising results in suppressing AF, alleviating post-MI ventricular arrhythmias and ischaemia-reperfusion injury along with improving diastolic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10390725/

Chronic vagus nerve stimulation in patients with heart failure Based on these encouraging experimental data, vagus nerve stimulation (VNS) has been assessed in patients with HF with a reduced ejection fraction.