Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function in PAD
Condition: Peripheral Artery Disease; Endothelial Dysfunction; Autonomic Imbalance
MeSH terms: Peripheral Arterial Disease
Study type: Interventional

Summary: 
      Peripheral arterial disease (PAD) constitutes a major public health burden. The incidence of
      PAD increases with age and is associated with other comorbid cardiovascular disorders.
      Atherosclerosis which underlies PAD is associated with increased arterial stiffness and an
      enhanced inflammatory state as evidenced by increased levels of pro-inflammatory cytokines
      and markers. One the earliest signs of cardiovascular disease is endothelial dysfunction
      which is characterized by a decreased vasodilatory capacity of the vascular endothelium and
      this lesion predates the development of clinical atherosclerosis. Endothelial dysfunction has
      been shown to be widely prevalent in PAD. It is postulated that endothelial dysfunction is
      due to enhanced sympathetic drive, diminished parasympathetic drive, chronic inflammatory
      state all of which leads to reduced nitric oxide synthase activity in the vascular
      endothelium with subsequent loss of vasodilatory capacity. Studies have shown endothelial
      dysfunction to be reversible with pharmaco-therapeutic interventions, though these
      interventions are associated with their own adverse effects. Stimulation of Vagal nerve
      increases the parasympathetic activity while suppressing sympathetic drive, decreases
      inflammation and enhancing nitric oxide synthase activity. Recent experimental and clinical
      data suggest that low-level tragus nerve stimulation (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 vagus nerve stimulation. It is however unknown if
      Transcutaneous Vagal Stimulation (TVS) would lead to improved endothelial function as
      measured by flow mediated dilatation (FMD) and laser speckle contrast imaging(LSCI), a
      non-invasive method of measuring endothelial function or decrease in arterial stiffness as
      measured by Pulse Wave Analysis (PWA), in patients with PAD. The objective of this study is
      to determine the impact of TVS on endothelial dysfunction as measured by FMD & LSCI and
      arterial stiffness. Study population will include patients with established diagnosis of PAD.
      After performing baseline FMD, LSCI and PWA patients will be randomized to TVS and sham
      stimulation with cross over. The patient randomized to TVS stimulation will obtain
      stimulation for 1 hour followed by 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.
    


Intervention name(s): TVS; Sham TVS
Intervention type(s): Device; Device
Intervention description(s): 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; Device will be applied but not to the Tragus of the ear but will be attached to the ear lobule.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment