Low Level Tragus Stimulation in Acute Decompensated Heart Failure

NCT02898181 | Recruiting DMC

• 1 other identifier: 6778
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Decompensated Heart Failure

Outcome Measures

Primary Outcomes (4)

• Change in Interleukin (IL) levels

  Interleukin level

  From admission to discharge- over average 3-6 days

• Change in TNF-alpha levels

  TNF level

  From admission to discharge- over average 3-6 days

• Change in CRP levels

  CRP level

  From admission to discharge- over average 3-6 days

• Change in Pro BNP and renal function(creatinine) levels

  Pro BNP level

  From admission to discharge- over average 3-6 days

Secondary Outcomes (1)

• Change in HRV

  From admission to discharge- over average 3-6 days

Other Outcomes (1)

• Change in level of dyspnea

  From admission to discharge- over average 3-6 days

Study Arms (2)

Tragus Stimulation

EXPERIMENTAL

In this group patients will receive neuromodulation for 2 hours daily

Device: Neuromodulation

Control group

NO INTERVENTION

Sham neuromodulation will be done

Interventions

Neuromodulation 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.

Tragus Stimulation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted with ADHF

You may not qualify if:

• Refusal to consent
• Complex congenital heart disease (Tetralogy of Fallot patients, single ventricle physiology)
• Recurrent vaso-vagal syncopal episodes
• Unilateral or bilateral vagotomy
• Sick sinus syndrome
• nd or 3rd degree AV block
• bifascicular block or prolonged 1st degree AV block (PR\>300ms)
• Pregnant patients
• Prisoners
• Advanced renal dysfunction(defined as eGFR \< 30, stage 4 or 5 chronic kidney disease)
• Hepatitis C or HIV
• Acute Myocardial infarction

Sponsors & Collaborators

• University of Oklahoma: lead

Study Sites (1)

OUHSC

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 37943335 DERIVED

• 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.

  PMID: 37790298 DERIVED

MeSH Terms

Interventions

Transcutaneous Electric Nerve Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

Study Officials

• Tarun Dasari, MD,MPH

  OUHSC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tarun Dasari, MD,MPH

CONTACT

4052714742; tdasari@ouhsc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 13, 2016
• Study Start: September 1, 2016
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)