Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in HFrEF
Primary Purpose
Heart Failure With Reduced Ejection Fraction, Endothelial Dysfunction
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
TVS
Sham TVS
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction
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:
- patients in overt congestive heart failure / recent acute myocardial infarction (< 3 months) or Unstable angina
- Active malignancy
- Perimenopausal women and post-menopausal women on hormone supplements.
- unilateral or bilateral vagotomy
- Patients with bilateral upper extremity amputation
- pregnant patients
- End-stage renal disease
- End-stage liver disease
- history of recurrent vasovagal syncope, Sick sinus syndrome, 2nd- or 3rd-degree atrioventricular (AV) block.
- patients with clinically documented upper extremity arterial disease
- patients with BMI>34
Sites / Locations
- University of Oklahoma Health Sciences Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Interventional
Control
Arm Description
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 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.
Outcomes
Primary Outcome Measures
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.
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).
Secondary Outcome Measures
LSCI
LSCI based perfusion index will be calculated before and within 30 minutes of TVS or sham stimulation
Full Information
NCT ID
NCT03380156
First Posted
October 12, 2017
Last Updated
January 13, 2021
Sponsor
University of Oklahoma
1. Study Identification
Unique Protocol Identification Number
NCT03380156
Brief Title
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
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
December 4, 2017 (Actual)
Primary Completion Date
May 30, 2020 (Actual)
Study Completion Date
May 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oklahoma
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction, Endothelial Dysfunction
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Blinding will be done so the investigator performing the FMD and PWA testing will be blinded to the allocation of TNS
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Interventional
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
TVS
Intervention Description
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
Intervention Name(s)
Sham TVS
Intervention Description
Device will be applied but not to the Tragus of the ear but will be attached to the ear lobule.
Primary Outcome Measure Information:
Title
Flow Mediated Vasodilation
Description
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.
Time Frame
Change from baseline to post stimulation(within 10 minutes) with TVNS/Sham stimulation
Title
Pulse Wave Analysis
Description
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).
Time Frame
Change from baseline to post stimulation(within 15-20 minutes) with TVNS/Sham stimulation
Secondary Outcome Measure Information:
Title
LSCI
Description
LSCI based perfusion index will be calculated before and within 30 minutes of TVS or sham stimulation
Time Frame
Change from baseline to post stimulation(within 30 minutes) with TVS/Sham stimulation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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:
patients in overt congestive heart failure / recent acute myocardial infarction (< 3 months) or Unstable angina
Active malignancy
Perimenopausal women and post-menopausal women on hormone supplements.
unilateral or bilateral vagotomy
Patients with bilateral upper extremity amputation
pregnant patients
End-stage renal disease
End-stage liver disease
history of recurrent vasovagal syncope, Sick sinus syndrome, 2nd- or 3rd-degree atrioventricular (AV) block.
patients with clinically documented upper extremity arterial disease
patients with BMI>34
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tarun Dasari, MD,MPH
Organizational Affiliation
OUHSC
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73117
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in HFrEF
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