Peripheral Artery DiseaseTVS-PADNCT03445754
Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function in PAD
A study testing TVS in people with Peripheral Artery Disease and Endothelial Dysfunction, run by University of Oklahoma at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Peripheral Artery Disease, Endothelial Dysfunction, Autonomic Imbalance
- What is being tested?
- TVS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2017to 30 May 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
- Patients with pacemakers who have significant interaction with TVNS during testing
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73117
About this study
Official title: Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in Peripheral Artery Disease
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.
- Being tested
- TVS, Sham TVS
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TVSDevice
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
Sham TVSDevice
Device will be applied but not to the Tragus of the ear but will be attached to the ear lobule.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Sham TVS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline to post stimulation(within 10 minutes of stimulation) with TVS/Sham stimulation
Secondary outcomes (2)
Endothelial function in microcirculation
LSCI based calculation of perfusion unit before and after TVS/Sham stimulation
Measured: Change from baseline to post stimulation(within 20-30 minutes of stimulation) with TVS/Sham stimulation
Pulse wave analysis
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).
Measured: Change from baseline to post stimulation(within 15-20 minutes) with TVS/Sham stimulation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2018
- Study start11 Dec 2017
- Primary completion30 May 2020
- Study completion30 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- More trials run by University of OklahomaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a pilot study.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tarun Dasari, MD, MPH, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03445754
- Sponsor's protocol ID
- 8473P
- Acronym
- TVS-PAD
- Status last verified
- Mar 2026
- First submitted
- 12 Oct 2017
- Last updated
- 1 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in Peripheral Artery Disease
- ClinicalTrials.gov ID
- NCT03445754
- Acronym / sponsor ID
- TVS-PAD / 8473P
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Study start
- 11 Dec 2017 (actual)
- Primary completion
- 30 May 2020 (actual)
- Study completion
- 30 May 2020 (actual)
- First posted
- 26 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a pilot study.
| Arm | Type | Receives |
|---|---|---|
| Interventional Arm | Experimental | Device: TVSActive 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. |
| Control | Sham comparator | Device: Sham TVSSham 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TVSActive 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 | Interventional Arm |
| Sham TVSDevice will be applied but not to the Tragus of the ear but will be attached to the ear lobule. | Device | Control |
Primary outcome
Flow mediated vasodilatation
Time frame: Change from baseline to post stimulation(within 10 minutes of stimulation) with TVS/Sham stimulation
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.
2 secondary outcomes
Endothelial function in microcirculation
Time frame: Change from baseline to post stimulation(within 20-30 minutes of stimulation) with TVS/Sham stimulation
Pulse wave analysis
Time frame: Change from baseline to post stimulation(within 15-20 minutes) with TVS/Sham stimulation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tarun Dasari, MD, MPH principal investigator
University of Oklahoma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TVS in people with Peripheral Artery Disease and Endothelial Dysfunction, run by University of Oklahoma at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Flow mediated vasodilatation (time frame: Change from baseline to post stimulation(within 10 minutes of stimulation) with TVS/Sham stimulation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026.