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

Endothelial Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03380156
• Other study ID #: 8469
• Status: Completed
• Phase: N/A
• Start date: December 4, 2017
• Est. completion date: May 30, 2020

Study information

• Verified date: January 2021
• Source: University of Oklahoma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 30, 2020
• Est. primary completion date: May 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Endothelial Dysfunction
• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

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
• Sham TVS
Device will be applied but not to the Tragus of the ear but will be attached to the ear lobule.

Locations

Country	Name	City	State
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
University of Oklahoma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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