Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function in PAD

NCT03445754 | Completed DMC FDA Device

• 1 other identifier: 8473P
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Peripheral Artery Disease; Endothelial Dysfunction; Autonomic Imbalance

Outcome Measures

Primary Outcomes (1)

• Flow mediated vasodilatation

  Flow mediated vasodilatation will be tested. A change in the maximal diameter of the brachial artery(in mm) will be assessed immediately(within 10 minutes) after TVNS/sham stimulation.

  Change from baseline to post stimulation(within 10 minutes of stimulation) with TVS/Sham stimulation

Secondary Outcomes (2)

• Endothelial function in microcirculation

  Change from baseline to post stimulation(within 20-30 minutes of stimulation) with TVS/Sham stimulation

• Pulse wave analysis

  Change from baseline to post stimulation(within 15-20 minutes) with TVS/Sham stimulation.

Study Arms (2)

Interventional Arm

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.

Device: TVS

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.

Device: Sham TVS

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

Interventional Arm

Sham TVS DEVICE

Device will be applied but not to the Tragus of the ear but will be attached to the ear lobule.

Control

Eligibility Criteria

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

You may qualify if:

• peripheral arterial disease (PAD) - patients with an ankle-brachial index of \<0.9
• symptoms of intermittent claudication, rest pain, or minor tissue loss (Rutherford category I-V)

You may not qualify if:

• patients with acute limb ischemia
• Patients with overt congestive heart failure / recent acute myocardial infarction (\< 3 months)
• Premenopausal women and post-menopausal women on hormone supplements.
• chronic inflammatory disease (systemic lupus erythematosus, rheumatoid arthritis, and Crohn's disease), or receiving therapy with steroids, cyclosporine, methotrexate or immunocompromised patients.
• unilateral or bilateral vagotomy
• Patients with bilateral upper extremity amputation
• pregnant patients
• prisoners
• end-stage renal disease.
• End-stage liver disease.
• patients with BMI\>34
• Patients with upper extremity arterial disease
• history of recurrent vasovagal syncope, Sick sinus syndrome, 2nd- or 3rd-degree atrioventricular block (AV) block, prolonged first degree AV block.
• Refusal to sign a consent form.
• Significant hypotension from autonomic dysfunction

Sponsors & Collaborators

• University of Oklahoma: lead

Study Sites (1)

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73117, United States

Location

MeSH Terms

Conditions

Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Study Officials

• Tarun Dasari, MD, MPH

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Blinding will be done so the investigator performing the FMD, LSCI and PWA testing will be blinded to the allocation of TVS
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot study.

Study Record Dates

• First Submitted: October 12, 2017
• First Posted: February 26, 2018
• Study Start: December 11, 2017
• Primary Completion: May 30, 2020
• Study Completion: May 30, 2020
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (1)