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

NCT ID: NCT03380156

Last Updated: 2021-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-04
• Study Completion Date: 2020-05-30

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.

Conditions

Heart Failure With Reduced Ejection Fraction; Endothelial Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

TVS

Intervention Type: DEVICE

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

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.

Group Type: PLACEBO_COMPARATOR

Sham TVS

Intervention Type: DEVICE

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

Interventions

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

Intervention Type: DEVICE

Sham TVS

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

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oklahoma

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tarun Dasari, MD,MPH

Role: PRINCIPAL_INVESTIGATOR

OUHSC

Locations

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Countries

United States

Other Identifiers

8469

Identifier Type: -

Identifier Source: org_study_id