Neuromodulation of Inflammation and Vascular Function in Systolic Heart Failure

NCT03945058 | Terminated DMC FDA Device

• 1 other identifier: 10410T
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure (HF) is the leading cause of death in US. It is associated with abnormal vascular function termed endothelial dysfunction. It is also associated with increased stress on the blood vessels and high levels of inflammation. Vagus nerve stimulation can help improve inflammation, vascular function and vascular stress. The investigator has recently completed a study showing that 1 hour of noninvasive vagus stimulation can improve vascular health. However, it is unknown if 4 weeks of stimulation will be beneficial in systolic heart failure. The purpose of this study is to determine if transcutaneous vagal stimulation (TVS) will lead to improvement in the function of the inner lining of participants' arteries, memory, and in the levels of certain chemical markers of arterial function in the blood. Participants will be randomized to receive either TVS or a sham stimulation and undergo 4 weeks of stimulation. Vascular function will be assessed by several non-invasive measurements, including Flow Mediate Dilation (FMD), Pulse Wave Analysis (PWA), EndoPAT, and Laser Speckle Contrast Imaging (LSCI). Participants' memory will also be measured through electronic assessments and blood will be collected and analyzed for arterial function chemical markers.

Conditions

Heart Failure With Reduced Ejection Fraction

Outcome Measures

Primary Outcomes (6)

• Flow Mediated Dilation (FMD)

  FMD is a change in the maximal diameter of the brachial artery. Brachial artery diameter (in millimeters) will be assessed before and after 4 weeks of stimulation using standard ultrasound.

  Change in the brachial artery diameter will be compared to baseline change after 4 weeks of TVS or sham.

• Laser Speckle Contrast Imaging (LSCI)

  LSCI based perfusion index and perfusion units will be calculated before and after 4 weeks of TVS or sham stimulation.

  Change in the perfusion units will be determined at baseline and after 4 weeks of TVS or sham stimulation.

• EndoPAT

  Hyperemia index measured with ENDOPAT will be calculated before and after 4 weeks of TVS. Hyperemia index will be calculated using the standard ENDOPAT technique using probes placed on bilateral finger.

  Change in the reactive hyperemia index from baseline and after 4 weeks of TVS or SHAM stimulation

• Pulse Wave Analysis (PWA)

  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 in the augmentation index will be calculated at baseline and after 4 weeks of TVS or sham stimulation.

• Biomarkers of inflammation

  Inflammatory cytokines will assayed at baseline and after 4 weeks of stimulation. Cytokines assayed : Il1B,IL-6,IL-17,TNF-a,TGF-b,CRP etc- expressed in pg/ml units).

  Change in these biomarkers(% change) over 4 weeks will be calculated.

• Biomarkers of endothelial function and oxidative stress

  Biomarkers of endothelial function and oxidative stress include: ORAC, HORAC scores expressed as %.

  Change in these biomarkers(%) over 4 weeks will be calculated.

Secondary Outcomes (1)

• Cognition

  Change in the cognition score , as assessed by the CANTAB method will be compared at baseline and after 4 weeks of TVS or sham stimulation.

Study Arms (2)

Experimental

EXPERIMENTAL

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 daily for 4 weeks.

Device: TVS; Device: SHAM

CONTROL

SHAM COMPARATOR

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 daily for 4weeks.

Device: TVS; Device: SHAM

Interventions

TVS 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 daily for 4 weeks

CONTROL; Experimental

SHAM DEVICE

Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the earl lobule. Stimulator will be applied continuously for 1 hour daily for 4 weeks.

CONTROL; Experimental

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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%.

You may not qualify if:

• Patients in overt congestive heart failure / recent acute myocardial infarction (\< 3 months) or Unstable angina
• Active malignancy
• Pre-menopausal 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 a body mass index (BMI) \>35
• Significant hypotension (blood pressure \<90mmHg) secondary to autonomic dysfunction

Sponsors & Collaborators

• University of Oklahoma: lead

Study Sites (1)

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Study Officials

• Taun Dasari, MD

  OUHSC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This was a pilot study that was terminated. The COVID pandemic prevented the enrollment of more participants.

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: May 10, 2019
• Study Start: February 4, 2020
• Primary Completion: March 16, 2020
• Study Completion: December 16, 2021
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)