Clinical trial NCT02898181: Low Level Tragus Stimulation in Acute Decompensated Heart Failure
Official title: Low Level Transcutaneous Tragus Stimulation to Reduce Inflammation, Dyspnea and Improve Heart Rate Variability in Acute Decompensated Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Decompensated Heart Failure
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
First posted: 2016-09-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Interleukin (IL) levels
timeFrame: From admission to discharge- over average 3-6 days
measure: Change in TNF-alpha levels
timeFrame: From admission to discharge- over average 3-6 days
measure: Change in CRP levels
timeFrame: From admission to discharge- over average 3-6 days
measure: Change in Pro BNP and renal function(creatinine) levels
timeFrame: From admission to discharge- over average 3-6 days
Secondary outcomes:
measure: Change in HRV
timeFrame: From admission to discharge- over average 3-6 days
Other outcomes:
measure: Change in level of dyspnea
timeFrame: From admission to discharge- over average 3-6 days
Locations:
city: Oklahoma City
country: United States
facility: OUHSC
state: Oklahoma
Study officials:
affiliation: OUHSC
name: Tarun Dasari, MD,MPH
role: PRINCIPAL_INVESTIGATOR
References: