Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in HFrEF

Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in Patients With Heart Failure With Reduced Ejection Fraction

Heart failure (HF) is the leading cause of hospitalization in the US. Endothelial dysfunction, characterized by the decreased vasodilatory capacity of the vascular endothelium, is rampant in atherosclerotic diseases such as coronary artery disease and also in HF. Endothelial dysfunction also correlates with HF severity, progression, and mortality. It is postulated that endothelial dysfunction may in part be due to enhanced sympathetic drive, diminished parasympathetic drive, chronic inflammatory state thereby leading to reduced nitric oxide synthase activity in the vascular endothelium. Low-level vagus nerve stimulation (LLVNS) is an invasive way to modulate autonomic tone. Recent experimental and clinical data suggest that low-level transcutaneous vagal stimulation (TVS) (by stimulating the auricular branch of the vagus nerve located at the tragus of the external ear) may produce the same desired neuromodulator effect compared to LLVNS. The objective of this study is to determine the impact of TVS on endothelial dysfunction and arterial stiffness. The study population will include patients with chronic HFrEF. After performing baseline flow-mediated dilation (FMD), laser speckle contrast imaging(LSCI) and pulse wave analysis (PWA) testing, patients will be randomized to TVS or sham stimulation with a crossover design at different time points. The patient randomized to TVS arm will undergo stimulation for 1 hour followed by immediate measurement of FMD,LSCI and PWA. There will be a washout period of at least 24 hours with patient crossing over to the other arms thus serving as their self-control.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction; Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Device: TVS; Device: Sham TVS

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients (18 years or older) with Heart failure with reduced ejection fraction (HFrEF), which is a history of symptomatic heart failure with left ventricular ejection fraction (LVEF) of < 40%.

Exclusion Criteria:

1. patients in overt congestive heart failure / recent acute myocardial infarction (< 3 months) or Unstable angina
2. Active malignancy
3. Perimenopausal women and post-menopausal women on hormone supplements.
4. unilateral or bilateral vagotomy
5. Patients with bilateral upper extremity amputation
6. pregnant patients
7. End-stage renal disease
8. End-stage liver disease
9. history of recurrent vasovagal syncope, Sick sinus syndrome, 2nd- or 3rd-degree atrioventricular (AV) block.
10. patients with clinically documented upper extremity arterial disease
11. patients with BMI>34

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Interventional; Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour.	Device: TVS; Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour
PLACEBO_COMPARATOR: Control; Sham TVS will be performed by use of a Tragus stimulator device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour.	Device: Sham TVS; Device will be applied but not to the Tragus of the ear but will be attached to the ear lobule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow Mediated Vasodilation	Flow mediated vasodilatation will be tested. A change in the maximal diameter of the brachial artery(in mm) will be assessed before and within 10 minutes of TVNS/sham stimulation.	Change from baseline to post stimulation(within 10 minutes) with TVNS/Sham stimulation
Pulse Wave Analysis	Arterial elasticity. Augmentation pressure (AP) will be calculated which is expressed as a percentage of the aortic pulse pressure (PP) which is the difference of systolic and diastolic BP(mm Hg).	Change from baseline to post stimulation(within 15-20 minutes) with TVNS/Sham stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LSCI	LSCI based perfusion index will be calculated before and within 30 minutes of TVS or sham stimulation	Change from baseline to post stimulation(within 30 minutes) with TVS/Sham stimulation

Collaborators and Investigators

• Sponsor: University of Oklahoma

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2017
• Primary Completion (ACTUAL): May 30, 2020
• Study Completion (ACTUAL): May 30, 2020

Study Registration Dates

• First Submitted: October 12, 2017
• First Submitted That Met QC Criteria: December 15, 2017
• First Posted (ACTUAL): December 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 13, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 8469

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No