Non-invasive Vagus Nerve Stimulation for Vaping

(nVNS Trial)

Recruiting at 1 trial location

Overseen By Vinay Parikh, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Temple University

Must not be taking: Hypertension meds, Arrhythmia meds

Disqualifiers: Pregnancy, Schizophrenia, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking medications for high blood pressure, irregular heartbeats, or calcium channel blockers, you cannot participate in this trial.

What data supports the effectiveness of the treatment nVNS for vaping?

Non-invasive vagus nerve stimulation (nVNS) has shown promise in treating various conditions, such as chronic migraines and treatment-resistant depression, by modulating the vagus nerve. This suggests potential for nVNS to be effective in other areas, like vaping, due to its ability to influence the nervous system safely and non-surgically. ^{1 2 3 4 5}

How does non-invasive vagus nerve stimulation (nVNS) differ from other treatments for vaping?

Non-invasive vagus nerve stimulation (nVNS) is unique because it uses a non-surgical, portable device to stimulate the vagus nerve, which is different from traditional treatments that might involve medication or behavioral therapy. This method is appealing as it is safe, inexpensive, and allows for rapid application without the need for surgery. ^{1 2 6 7 8}

What is the purpose of this trial?

The purpose of this study is to assess the effects of non-invasive vagus nerve stimulation (nNVS) on cognitive functioning in the users of e-cigarettes or vaping products. The investigators will use a digital wellness companion product (TRUVAGA™ device) that provides mild transcutaneous nVNS. The participants will be randomized to receive either a 2-min nNVS stimulation or control stimulation in the neck region followed by completion of two cognitive tests of attention.

Research Team

Vinay Parikh, PhD

Principal Investigator

Temple University

Jason Chein, PhD

Principal Investigator

Temple University

Tania Giovannetti, PhD

Principal Investigator

Temple University

Eligibility Criteria

This trial is for young adults who use e-cigarettes or vaping products. Participants will be tested to see if a non-invasive device that stimulates the vagus nerve can affect their attention and cognitive functioning.

Inclusion Criteria

Current or prior users of e-cigarettes

I am a healthy young adult.

Exclusion Criteria

I have a rash, infection, swelling, cut, soreness, drug patch, or surgical scar on my neck.

Have any implantable medical device in their body such as a pacemaker, hearing aid implant, or any other metallic/electronic device

Are pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either a 2-min nNVS stimulation or control stimulation in the neck region followed by cognitive tests

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• nVNS

Trial Overview The study tests a digital wellness device (TRUVAGA™) providing mild stimulation to the vagus nerve through the skin. Participants are randomly assigned to receive either an active 2-minute stimulation or a placebo-like control, followed by cognitive tests.

Participant Groups

Group I: Control Stimulation Experimental Treatment 1 Intervention

Participants in the control arm will receive a 2-min transcutaneous stimulation using a portable hand-held digital wellness Truvaga Plus device by placing it on the posterolateral part of the neck (near the overlapping area between the trapezeus muscle and the shoulder).

Group II: Active Stimulation Experimental Treatment 1 Intervention

Participants in the active arm will receive a 2-min transcutaneous vagus nerve stimulation using a portable hand-held digital wellness Truvaga Plus device by placing it on the anterolateral cervical area of the neck.

Who Is Running the Clinical Trial?

Temple University

Lead Sponsor

Trials

321

Recruited

89,100+

Findings from Research

In a study involving 28 healthy participants, noninvasive vagal nerve stimulation (nVNS) significantly reduced lacrimation compared to no stimulation and one type of sham stimulation, indicating its potential efficacy in modulating autonomic responses.

However, the study found that the sham device also produced similar effects, suggesting that both nVNS and the sham device can influence the trigeminal-autonomic reflex, which may explain the high placebo effects seen in previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nVNS sham significantly affects the trigeminal-autonomic reflex: A randomized controlled study. Schroeder, CF., Möller, M., May, A.[2020]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Noninvasive vagus nerve stimulation (nVNS) was found to be safe and well-tolerated in a pilot study involving 59 adults with chronic migraine, with most adverse events being mild and transient.

While nVNS did not show a significant reduction in headache days compared to sham treatment during the randomized phase, participants who continued with nVNS in the open-label phase experienced a meaningful decrease in headache days after 8 months, suggesting potential long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. Silberstein, SD., Calhoun, AH., Lipton, RB., et al.[2022]

In a study involving 15 patients with chronic pelvic pain due to endometriosis, respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) showed a trend towards reducing pain intensity and significantly decreased anxiety compared to nonvagal auricular stimulation (NVAS).

RAVANS demonstrated moderate to large effect sizes in reducing pain and anxiety, suggesting it could be a promising nonpharmacological treatment option for chronic pain disorders, warranting further investigation into its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. Napadow, V., Edwards, RR., Cahalan, CM., et al.[2022]

Vagus nerve stimulation (VNS) is an FDA-approved treatment for epilepsy, morbid obesity, and treatment-resistant depression, but it is often underutilized due to high costs and the need for surgical implantation.

The development of transcutaneous auricular VNS (taVNS) offers a promising noninvasive alternative that could provide a safe, at-home treatment option for various neuropsychiatric disorders, with ongoing trials like the RECOVER trial evaluating its efficacy in treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Future Is Noninvasive: A Brief Review of the Evolution and Clinical Utility of Vagus Nerve Stimulation. Badran, BW., Austelle, CW.[2023]

A high-resolution model of cervical non-invasive vagus nerve stimulation (nVNS) was developed using MRI-derived Finite Element Method (FEM) to accurately predict how different types of vagus nerve fibers are activated, showing that both macro and mesoscopic anatomical details are crucial for accurate predictions.

The model predicts that conventional nVNS protocols can effectively activate A- and B-fibers, which are important for therapeutic effects, but not C-fibers, highlighting the need for precise modeling in optimizing vagus nerve stimulation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Resolution Multi-Scale Computational Model for Non-Invasive Cervical Vagus Nerve Stimulation. Mourdoukoutas, AP., Truong, DQ., Adair, DK., et al.[2022]

Selective stimulation of specific populations of vagal afferents using a multi-contact cuff electrode was successfully demonstrated in six ferrets, allowing targeted activation of vagal neurons without affecting other organs.

Abdominal vagus nerve stimulation (VNS) was shown to selectively alter gastric myoelectric activity, indicating its potential as a therapeutic approach for controlling gastrointestinal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes. Shulgach, JA., Beam, DW., Nanivadekar, AC., et al.[2022]

This study reports the first-ever recordings from the human cervical vagus nerve using ultrasound-guided tungsten microelectrodes, allowing for a deeper understanding of its physiology in awake humans.

The recordings revealed that certain neurons in the vagus nerve are tonically active and their firing rates are inversely related to heart rate, suggesting their role as preganglionic parasympathetic axons that influence heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo recordings from the human vagus nerve using ultrasound-guided microneurography. Ottaviani, MM., Wright, L., Dawood, T., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

nVNS sham significantly affects the trigeminal-autonomic reflex: A randomized controlled study. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The Future Is Noninvasive: A Brief Review of the Evolution and Clinical Utility of Vagus Nerve Stimulation. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

High-Resolution Multi-Scale Computational Model for Non-Invasive Cervical Vagus Nerve Stimulation. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes. [2022]

8. England pubmed.ncbi.nlm.nih.gov

In vivo recordings from the human vagus nerve using ultrasound-guided microneurography. [2021]