Neuromodulation Therapy for Heart Failure

Overseen By Tarun Dasari, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

Disqualifiers: Congestive heart failure, Unstable angina, Active malignancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

158 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with heart failure with reduced ejection fraction (HFrEF), where the heart doesn't pump blood effectively. Researchers aim to determine if the Tragus Stimulator, a device that gently stimulates the vagus nerve in the ear, can reduce symptoms, improve exercise ability, and enhance quality of life. The trial includes two groups: one receiving actual nerve stimulation and the other receiving a sham (placebo-like) treatment. It seeks participants with heart failure and an ejection fraction of 50% or lower, excluding those with recent severe heart issues or other serious conditions. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve future heart failure treatments.

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 is best to consult with the trial coordinators for specific guidance.

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

Research shows that the tragus stimulator, which uses gentle electrical pulses on the vagus nerve, holds promise as a safe treatment. Studies have found that this method, which alters nerve activity, is well tolerated by individuals with heart conditions. Participants in earlier studies did not experience any serious side effects, indicating it could be a safe option for those with heart failure.

One large review found low-level tragus nerve stimulation to be both safe and well-tolerated. A smaller study suggested that this treatment might help reduce inflammation in the body, which benefits heart health. Overall, evidence suggests that the tragus stimulator is a safe treatment under study for heart failure. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for heart failure, which typically involve medications like ACE inhibitors, beta-blockers, and diuretics, the tragus stimulator offers a non-drug approach. This treatment is unique because it uses a neuromodulation device that targets the vagus nerve through the tragus of the ear. Researchers are excited about this therapy due to its potential to improve heart function without the side effects commonly associated with medication. Plus, its easy-to-use daily application could make it a convenient option for patients.

What evidence suggests that this neuromodulation therapy is effective for heart failure?

This trial will compare the effects of low-level tragus stimulation (LLTS) with a sham procedure in managing heart failure. Studies have shown that LLTS can help manage heart failure by affecting the vagus nerve, which plays a crucial role in controlling inflammation and heart function. In people with heart failure, LLTS has been linked to improved heart function and overall well-being. Specifically, one study found that LLTS reduced systemic inflammation, a major issue in heart failure, and helped control blood pressure in those with hypertension. These findings suggest that LLTS could be a promising treatment for people with heart failure, potentially enhancing their quality of life and heart health. ^{1 2 5 6 7}

Who Is on the Research Team?

Tarun Dasari, MD, MPH

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for adults with heart failure where the heart's pumping ability is reduced (EF ≤ 50%). It's not suitable for pregnant individuals, those with severe liver disease, recent heart attacks or unstable angina, active cancer, certain nerve surgeries (vagotomy), frequent fainting due to low blood pressure, specific irregular heartbeat conditions without a pacemaker, or dangerously low blood pressure from autonomic dysfunction.

Inclusion Criteria

My heart's pumping ability is reduced (EF ≤ 50%).

Exclusion Criteria

Pregnant patients

I have a history of fainting spells or heart rhythm problems without a pacemaker.

I do not have recent severe heart issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either active or sham LLTS for 1 hour daily over 12 weeks

12 weeks

Daily sessions (self-administered)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• SHAM
• Tragus Stimulator

Trial Overview The study tests if a neuromodulation device that stimulates the vagus nerve can improve symptoms and quality of life in patients with heart failure. Participants will use this device for an hour daily over three months and compare it against a sham (fake) treatment to measure effects on exercise capacity, inflammation levels and endothelial function.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

Active LLTS will be performed by use of a neuromodulation device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 12 weeks.

Group II: Control arm Placebo Group 1 Intervention

Sham LLTS will be performed by use of a neuromodulation device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour daily for 12 weeks.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., 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]

Neuromodulation therapies, such as spinal cord stimulation and vagus nerve stimulation, have shown promise in restoring autonomic balance in heart failure patients, which is crucial given the disease's association with sympathetic hyperactivity and parasympathetic hypoactivity.

Preclinical studies and early clinical trials indicate that these neuromodulatory treatments are both safe and effective, offering new hope for managing heart failure, a condition with high mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventional and device-based autonomic modulation in heart failure. Shen, MJ., Zipes, DP.[2015]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2772930323012012

Neuromodulation Therapies in Heart Failure: A State-of-the ... In this review, we provide a comprehensive overview of device-based therapeutics targeting the autonomic nervous system in patients with HF syndromes.

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

Low Level Tragus Stimulation in Acute Decompensated ... It is associated with increased systemic inflammation and poor outcomes. Previous studies have demonstrated increased inflammation in patients with heart ...

3. 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10543293/

Noninvasive low-level tragus stimulation attenuates ... In this proof-of-concept pilot study, in acute systolic heart failure, neuromodulation was feasible and safe and was associated with a reduction in systemic ...

5. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.032269

Low‐Level Tragus Stimulation Attenuates Blood Pressure ... LL‐TS led to significant blood pressure reductions in young patients with essential hypertension. Further larger trials are needed to confirm the safety and ...

6. jacc.org jacc.org/doi/10.1016/S0735-1097%2824%2902168-5

FIRST REPORT OF SAFETY AND TOLERABILITY OF LOW ... LLTVN appeared to be a safe and well tolerated intervention in patients with CVDs. This data represents the largest analysis of safety of LLTVN in CVD to date.

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.