Clinical trial NCT04682704: The Effect of Different Low-Level Tragus Stimulation Parameters On Autonomic Nervous System Function
Official title: The Effect of Different Low-Level Tragus Stimulation Parameters On Autonomic Nervous System Function
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Heart Failure, Diastolic
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
First posted: 2020-12-24
Enrollment: 90
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Low level transcutaneous vagus nerve stimulation (LLTS) involves delivery of electrical impulses transcutaneously at the auricular branch of vagus nerve and it has been shown to have anti-inflammatory and anti-arrhythmic effects. In previous studies from our laboratory, we found that LLTS significantly suppressed atrial fibrillation (AF) inducibility and decreased AF duration. The anti-arrhythmic effects of LLTS were similar to those delivered to the cervical VN trunk. LLTS for just one hour significantly shortened the AF duration and decreased inflammatory cytokines. We have also shown that LLTS leads to favorable heart rate variability (HRV) changes and cardiac mechanics in patients with diastolic dysfunction. These results support the use of LLTS as a novel non-pharmacological, non-ablative treatment modality for AF and possibly other inflammatory conditions. However, the optimal stimulation parameters of LLTS remain to be determined.

In this study, we aim to examine the effect of 2 different frequencies (5Hz and 20Hz) and 2 different amplitudes (50% below the pain threshold and 1mA below the pain threshold) of LLTS on heart rate variability with deep breathing (HRVdb), mental arithmetic stress test (MAST), frequency domain measures of heart rate variability (HRV) and brain stem evoked potentials (BSEVP) in healthy volunteers and patients with AF or heart failure with preserved ejection fraction (HFpEF). HRV is a marker of vagus nerve activity and can be easily measured by software calculating the distance between consecutive R waves on the ECG. BSEVP are a surrogate for the central projections of the vagus nerve. Patients will be randomized into 4 groups in a 2x2 factorial design. LLTS will be delivered through a transcutaneous electrical nerve stimulation (TENS) device for 15 minutes. HRVdb, HRV and BSEVP will be measured before and after LLTS and compared.


Eligibility criteria: Inclusion Criteria:

1. Male and female patients older than 21 year old
2. Healthy volunteers free from diagnosis of AF, heart failure, coronary artery disease or diseases that affect the autonomic nervous system.
3. Patients with Paroxysmal Atrial Fibrillation
4. Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)

Exclusion Criteria:

1. Recent (\<6 months) stroke
2. Recent (\<6 months) myocardial infarction
3. Heart failure (NYHA class III or IV)
4. Left ventricular ejection fraction \<50%
5. Recurrent vaso-vagal syncopal episodes
6. Unilateral or bilateral vagotomy
7. Pregnancy or breast feeding
8. Uncontrolled diabetes or hypertension
9. Inability or unwillingness to understand and/or sign informed consent
10. Any serious disease that affects autonomic nervous system function
11. Any medications that affect autonomic nervous system function

Primary outcomes:
measure: Heart rate variability
timeFrame: 15 minutes
measure: Mental arithmetic stress test
timeFrame: 15 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: Stavros Stavrakis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: