Low Level Tragus Stimulation in Acute Decompensated Heart Failure

NCT ID: NCT02898181

Last Updated: 2025-05-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2026-09-30

Brief Summary

Acute Decompensated Heart Failure (ADHF) is a major cause of morbidity and mortality. It is associated with increased systemic inflammation. Previous studies have demonstrated increased levels of cytokines such as C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10) and Tumor Necrosis Factor alpha (TNFα) in patients with heart failure (HF). Increased activity of sympathetic nervous system in ADHF is linked to inflammation. Previous anti-inflammatory drug therapies in HF have demonstrated no significant impact on cardiovascular outcomes. Low-level vagus nerve stimulation (LLVNS) is a non-invasive way to modulate autonomic tone and thereby inflammation. Vagal nerve stimulation is thought to increase the parasympathetic activity and suppress the sympathetic activity. Clinical studies of vagal stimulation in chronic HF have been negative. Recent experimental and clinical data suggest that low level tragus nerve stimulation (LLTNS) may produce the same desired neuromodulator effect compared to LLVNS. It is however unknown if LLTNS in ADHF will directly lead to a reduction in the levels of pro-inflammatory cytokines (CRP, IL-1, IL-6 and TNF-α) and an increase in the level of anti-inflammatory marker IL-10. heart rate variability may also be abnormal in ADHF. The objective of this proposal is to determine the impact of LLTS on inflammatory cytokines, heart failure biomarkers(Pro BNP) and HRV in patients with ADHF.In addition we will study the impact on dyspnea resolution and change in renal function during hospitalization.

Patients will be randomized to either active or sham stimulation (2 hours daily). Serum collected will (post-admission and discharge day) will be used for cytokine measurement. We will also measure daily ECG to assess HRV and patient assessed dyspnea scale.This investigation will likely establish the first evidence of the effects of LLTS on the suppression of inflammation and improvement in dyspnea, natriuretic peptides, renal function and HRV in patients presenting with ADHF.

Detailed Description

Acute Decompensated Heart Failure (ADHF) is a major cause of morbidity and mortality. It is associated with increased systemic inflammation and poor outcomes.

Previous studies have demonstrated increased inflammation in patients with heart failure (HF). Increased activity of sympathetic nervous system in ADHF is linked to inflammation. Previous anti-inflammatory drug therapies in HF have demonstrated no significant impact on cardiovascular outcomes.

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 stimulation is thought to increase the parasympathetic activity and suppress the sympathetic activity. Recent experimental and clinical data suggest that low level tragus nerve stimulation (LLTS) may produce the same desired neuromodulator effect compared to LLVNS.

It is however unknown if LLTS in ADHF will directly lead to sympathetic tone reduction and increase in parasympathetic tone, or neuromodulation and lead to reduction in the levels of pro-inflammatory cytokines (CRP, IL-1, IL-6 and TNF-α) and an increase in the level of anti-inflammatory marker IL-10.

Autonomic tone could be assessed using heart rate variability. The objective of this proposal is to determine the impact of LLTS on inflammatory cytokines and HRV in patients with ADHF.

Patients will be randomized to either active or sham stimulation (2 hours daily).

Serum collected will (post admission and discharge day) will be used for cytokine and biomarker measurement. We will also measure 10-15 minute ECG to assess HRV. Dyspnea will be determined using patient assessment tool(visual analog scale).This investigation will likely establish the first evidence of effects of LLTS on suppression of inflammation and improvement in dyspnea scale, renal function and HRV in patients presenting with ADHF.

Conditions

Acute Decompensated Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Tragus Stimulation

In this group patients will receive neuromodulation for 2 hours daily

Group Type: EXPERIMENTAL

Neuromodulation

Intervention Type: DEVICE

Active LLTS will be performed by use of a transcutaneous electrical nerve stimulation Parasym neuromodulation system with electrodes attached to the ear. Neuromodulation will be applied continuously for 2 hours daily.

Control group

Sham neuromodulation will be done

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Neuromodulation

Active LLTS will be performed by use of a transcutaneous electrical nerve stimulation Parasym neuromodulation system with electrodes attached to the ear. Neuromodulation will be applied continuously for 2 hours daily.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

Patients admitted with ADHF

Exclusion Criteria

1. Refusal to consent

2. Complex congenital heart disease (Tetralogy of Fallot patients, single ventricle physiology)

3. Recurrent vaso-vagal syncopal episodes

4. Unilateral or bilateral vagotomy

5. Sick sinus syndrome

6. 2nd or 3rd degree AV block

7. bifascicular block or prolonged 1st degree AV block (PR>300ms)

8. Pregnant patients

9. Prisoners

10. Advanced renal dysfunction(defined as eGFR < 30, stage 4 or 5 chronic kidney disease)

11. Hepatitis C or HIV

12. Acute Myocardial infarction

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oklahoma

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tarun Dasari, MD,MPH

Role: PRINCIPAL_INVESTIGATOR

OUHSC

Locations

OUHSC

Oklahoma City, Oklahoma, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Tarun Dasari, MD,MPH

Role: CONTACT

tdasari@ouhsc.edu

4052714742 ext. 44761

Facility Contacts

Tarun Dasari

Role: primary

tdasari@ouhsc.edu

405-271-4742 ext. 44761

Michael Stout

Role: backup

michael-stout@ouhsc.edu

4052714742 ext. 44761

References

Dasari TW, Chakraborty P, Mukli P, Akhtar K, Yabluchanskiy A, Cunningham MW, Csiszar A, Po SS. Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure. Clin Auton Res. 2023 Dec;33(6):767-775. doi: 10.1007/s10286-023-00997-z. Epub 2023 Nov 9.

Reference Type: DERIVED

PMID: 37943335 (View on PubMed)

Dasari T, Chakraborty P, Mukli P, Akhtar K, Yabluchanskiy A, Cunningham MW, Csiszar A, Po SS. Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure. Res Sq [Preprint]. 2023 Sep 11:rs.3.rs-3323086. doi: 10.21203/rs.3.rs-3323086/v1.

Reference Type: DERIVED

PMID: 37790298 (View on PubMed)

Other Identifiers

6778

Identifier Type: -

Identifier Source: org_study_id