Effect of Neuromodulation on Inflammation, Endothelial Function and Cognitive Dysfunction in Patients With Heart Failure With Reduced Ejection Fraction
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Laser Speckle Contrast Imaging (LSCI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: TVS (Device)
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.
干预措施: SHAM (Device)
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 daily for 4weeks.
干预措施: TVS (Device)
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 daily for 4weeks.
干预措施: SHAM (Device)
结局指标
主要结局
Laser Speckle Contrast Imaging (LSCI)
时间窗: Change in the perfusion units will be determined at baseline and after 4 weeks of TVS or sham stimulation.
LSCI based perfusion index and perfusion units will be calculated before and after 4 weeks of TVS or sham stimulation.
EndoPAT
时间窗: Change in the reactive hyperemia index from baseline and after 4 weeks of TVS or SHAM stimulation
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.
Biomarkers of inflammation
时间窗: Change in these biomarkers(% change) over 4 weeks will be calculated.
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).
Flow Mediated Dilation (FMD)
时间窗: Change in the brachial artery diameter will be compared to baseline change after 4 weeks of TVS or sham.
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.
Pulse Wave Analysis (PWA)
时间窗: Change in the augmentation index will be calculated at baseline and after 4 weeks of TVS or sham stimulation.
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).
Biomarkers of endothelial function and oxidative stress
时间窗: Change in these biomarkers(%) over 4 weeks will be calculated.
Biomarkers of endothelial function and oxidative stress include: ORAC, HORAC scores expressed as %.
次要结局
- 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.)