Clinical trial NCT03945058: Neuromodulation of Inflammation and Vascular Function in Systolic Heart Failure
Official title: Effect of Neuromodulation on Inflammation, Endothelial Function and Cognitive Dysfunction in Patients With Heart Failure With Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Heart Failure With Reduced Ejection Fraction
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
First posted: 2019-05-10
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Visit 1: Following tests(to assess vascular function) will be done: 1. FMD 2) LSCI 3) EndoPAT and 4) Pulse wave analysis (PWA). Patients will rest for 10 minutes between each test. They will be trained to use PARASYMTM unit for TVS. Blood collected, serum/plasma will be stored at -80F. Whole blood will be collected in PAXgene tubes. Patients will be instructed to apply TVS to either ear lobule (SHAM) or Tragus(experimental arm). Baseline characteristics will be collected including data on ventricular function(LVEF and left ventricular volumes).

Visit 2 (4 weeks): Follow up tests(FMD,LSCI,EndoPAT,PWA) and repeat blood collection.

Inflammatory cytokines and vascular function assays will be performed.

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. Pre-menopausal 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 a body mass index (BMI) \>35
12. Significant hypotension (blood pressure \<90mmHg) secondary to autonomic dysfunction

Primary outcomes:
measure: Flow Mediated Dilation (FMD)
timeFrame: Change in the brachial artery diameter will be compared to baseline change after 4 weeks of TVS or sham.
measure: Laser Speckle Contrast Imaging (LSCI)
timeFrame: Change in the perfusion units will be determined at baseline and after 4 weeks of TVS or sham stimulation.
measure: EndoPAT
timeFrame: Change in the reactive hyperemia index from baseline and after 4 weeks of TVS or SHAM stimulation
measure: Pulse Wave Analysis (PWA)
timeFrame: Change in the augmentation index will be calculated at baseline and after 4 weeks of TVS or sham stimulation.
measure: Biomarkers of inflammation
timeFrame: Change in these biomarkers(% change) over 4 weeks will be calculated.
measure: Biomarkers of endothelial function and oxidative stress
timeFrame: Change in these biomarkers(%) over 4 weeks will be calculated.
Secondary outcomes:
measure: Cognition
timeFrame: 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.
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
Study officials:
affiliation: OUHSC
name: Taun Dasari, MD
role: PRINCIPAL_INVESTIGATOR
References: