Clinical trial NCT03380156: Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in HFrEF
Official title: Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in Patients With Heart Failure With Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure With Reduced Ejection Fraction
Endothelial Dysfunction
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
First posted: 2017-12-20
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Flow Mediated Vasodilation
timeFrame: Change from baseline to post stimulation(within 10 minutes) with TVNS/Sham stimulation
measure: Pulse Wave Analysis
timeFrame: Change from baseline to post stimulation(within 15-20 minutes) with TVNS/Sham stimulation
Secondary outcomes:
measure: LSCI
timeFrame: Change from baseline to post stimulation(within 30 minutes) with TVS/Sham stimulation
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
Study officials:
affiliation: OUHSC
name: Tarun Dasari, MD,MPH
role: PRINCIPAL_INVESTIGATOR
References: