158 Participants Needed

Neuromodulation Therapy for Heart Failure

TD
CA
TD
Overseen ByTarun Dasari, MD, MPH
Age: 18+
Sex: Any
Trial Phase: Academic
Sponsor: University of Oklahoma
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

Heart failure with reduced ejection fraction (HFrEF) is a major cause of mortality in United States. Aging is a major risk factor for adverse outcomes associated with HFrEF, with majority of the patient's over the age of 50, continuing to experience symptoms, reduced exercise capacity and poor quality of life. We have previously demonstrated that low level transcutaneous electrical stimulation of the vagus nerve at the tragus (LLTS) suppresses inflammation in patients with atrial fibrillation and diastolic dysfunction and improved endothelial dysfunction in patients with chronic heart failure. The overall objective of this proposal is to examine the effects of LLTS on heart failure symptoms, exercise capacity and quality of life in patients with HFrEF and simultaneously determine the impact of LLTS on the suppression of inflammation and improvement in endothelial function. Our specific aims include: 1. To examine the medium term effect of intermittent (1 hour daily for 3 months) LLTS on exercise capacity and quality of life, related to sham stimulation, in patients with HFrEF, 2. To determine the effects of medium-term LLTS on sympathovagal/autonomic balance (assessed by heart rate variability) and systemic inflammation in patients with HFrEF and 3. To determine the effects of medium-term LLTS on endothelial function in patients with HFrEF. The proposed proof-of-concept human studies will provide the basis for the design of further human studies using LLTS among larger populations with HFrEF. In light of the increasing number of elderly patients who continue to experience HFrEF symptoms, recognized is a key point of interest in this funding mechanism, and the suboptimal success of the currently available treatment options to ameliorate the problems mentioned above, an alternative novel approach such as LLTS has the potential to impact clinical practice and improve health outcomes among the large number of patients. It is anticipated that these investigations will contribute to a broader understanding of the role of autonomic imbalance, inflammation and endothelial dysfunction in the pathogenesis of HFrEF and how its inhibition can be used to provide therapeutic effects. Moreover, it is anticipated that a better understanding of how modulation of autonomic tone, inflammation and endothelial function affects one of the hallmarks of HFrEF will lead to the development of normal nonpharmacological and pharmacological approaches to treat this disease.

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 data supports the effectiveness of the treatment SHAM, Tragus Stimulator for heart failure?

Research shows that low-level tragus stimulation (LLTS) can help improve heart function by reducing inflammation and stress in heart failure patients. It has also shown promise in treating other heart-related issues like arrhythmias and heart attacks, suggesting it could be beneficial for heart failure.12345

Is neuromodulation therapy for heart failure safe for humans?

Neuromodulation therapy, like low-level tragus stimulation (LLTS) and transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe in humans. Most studies report only mild and temporary side effects such as ear pain, headache, and tingling, with no severe adverse events linked to the treatment.23567

How does the Tragus Stimulator treatment for heart failure differ from other treatments?

The Tragus Stimulator is unique because it is a non-invasive treatment that uses low-level stimulation of the tragus (a part of the ear) to modulate the nervous system, aiming to restore balance between the sympathetic and parasympathetic systems. This approach is different from traditional heart failure treatments, which often involve medications or invasive procedures, as it targets the neuro-immune axis to reduce inflammation and oxidative stress.23489

Research Team

TD

Tarun Dasari, MD, MPH

Principal Investigator

University of Oklahoma

Eligibility Criteria

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.
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Timeline

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)

Treatment Details

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.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: ExperimentalExperimental Treatment1 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 armPlacebo Group1 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.

Find a Clinic Near You

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+

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

References

Effects of Low-Level Tragus Stimulation on Endothelial Function in Heart Failure With Reduced Ejection Fraction. [2023]
Non-invasive Low-level Tragus Stimulation in Cardiovascular Diseases. [2020]
Chronic Intermittent Low-Level Stimulation of Tragus Reduces Cardiac Autonomic Remodeling and Ventricular Arrhythmia Inducibility in a Post-Infarction Canine Model. [2021]
Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure. [2023]
Low-Level Tragus Stimulation for the Treatment of Ischemia and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: A Proof-of-Concept Study. [2019]
Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]
Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure. [2021]
Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure. [2023]
Interventional and device-based autonomic modulation in heart failure. [2015]