Vagus Nerve Stimulation for Sleep

Overseen By Marc J Poulin, PhD, DPhil, FPhysiol

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Disqualifiers: Obesity, Heart disease, Diabetes, others

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

Compensation: Varies

Number of Visits: 5

Duration: 4 nights

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a small, battery-operated device can improve sleep and overall daily life quality. The device gently stimulates the vagus nerve through the outer ear for 30 minutes, a method known as non-invasive vagus nerve stimulation. Participants will undergo two sessions: one with the device on and another with it off, to assess any differences in sleep quality. This trial may suit healthy adults under 50 who are comfortable using ear and sleep monitoring devices at home. As an unphased trial, it offers participants the chance to contribute to innovative research that could enhance sleep quality for many.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that this device is safe for improving sleep?

A previous study tested the safety of transcutaneous vagus nerve stimulation (t-VNS) and found it generally well-tolerated, with no major side effects reported. Another study confirmed its safety by comparing it to a placebo treatment, ensuring the effects were genuine. Most participants did not experience harmful side effects.

This treatment uses a device that operates externally, which is generally safer as it avoids surgical risks. Overall, research suggests that this type of nerve stimulation is safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about non-invasive vagus nerve stimulation for sleep because it offers a novel approach compared to traditional treatments like cognitive behavioral therapy, medications, or lifestyle changes. Unlike these traditional methods, this treatment uses a battery-operated device attached to the outer ear, which may enhance sleep quality by increasing vagal tone and baroreflex sensitivity. This non-invasive delivery method could lead to improved sleep and quality of life without the need for drugs or intensive therapy, making it a potentially game-changing option for those struggling with sleep issues.

What evidence suggests that this device is effective for improving sleep?

Research has shown that a gentle, non-invasive method to stimulate the vagus nerve, called taVNS, can greatly improve sleep quality. In this trial, participants will use a battery-operated portable device attached to the outer ears to test its effectiveness on sleep and quality of life. Some studies have found that this treatment can lessen the severity of insomnia and improve overall quality of life compared to a placebo. In one study, taVNS led to a 50% reduction in sleep issues, as measured by the Pittsburgh Sleep Quality Index. Additionally, taVNS has effectively helped people with post-traumatic stress disorder (PTSD) sleep better, highlighting its potential benefits. Overall, these findings suggest that taVNS is a promising way to enhance sleep. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for healthy volunteers interested in improving their sleep. Participants will be required to visit the lab twice, three weeks apart, and use a sleep kit at home. There are no specific inclusion or exclusion criteria provided.

Inclusion Criteria

Ability to provide informed consent and willingness to comply with the study procedures

I can breathe through my nose easily and can wear a sleep monitor.

I am in good health with no major medical issues.

Exclusion Criteria

Current smoker

Pregnancy or lactation due to the location of the sleep devices

Resting heart rate > 120 bpm

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 hour

1 visit (in-person)

Treatment

Participants receive neuromodulation stimulation and self-instrument the sleep monitoring kit at home for 4 nights

4 nights

2 visits (in-person) for setup and return of equipment

Washout

21-day washout period between treatment sessions

3 weeks

Re-treatment

Re-assessment of neuromodulation stimulation level and re-issue of sleep kit for another 4 nights

4 nights

2 visits (in-person) for setup and return of equipment

Follow-up

Participants are monitored for changes in sleep quality and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Non-invasive Vagus Nerve Stimulation

Trial Overview The study tests if a portable device that stimulates the vagus nerve through the outer ear can enhance sleep quality. The device's effects on sleep will be measured using a PSG (polysomnography) device during two separate sessions.

How Is the Trial Designed?

Group I: Trial Arm 2 Experimental Treatment 1 Intervention

Participants and experimenters are blinded. The aim of this study is to determine whether a battery-operated portable device (current adjustable) attached to the outer ears (tragus) makes one more likely to improve on their sleep and quality of daily life. Investigators believe this device encourages increases in vagal tone associated with increases in baroreflex sensitivity, improving sleep and possibly leading to an increase in quality of life.

Group II: Trial Arm 1 Experimental Treatment 1 Intervention

Participants and experimenters are blinded. The aim of this study is to determine whether a battery-operated portable device (current adjustable) attached to the outer ears (tragus) makes one more likely to improve on their sleep and quality of daily life. Investigators believe this device encourages increases in vagal tone associated with increases in baroreflex sensitivity, improving sleep and possibly leading to an increase in quality of life.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Natural Sciences and Engineering Research Council, Canada

Collaborator

Trials

63

Recruited

3,000+

Published Research Related to This Trial

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]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved sleep quality and structure in 21 patients with primary insomnia over a 4-week treatment period, as measured by the Pittsburgh Sleep Quality Index and various sleep metrics.

The treatment led to increased sleep efficiency and deeper sleep stages, along with enhanced nocturnal heart rate variability, suggesting that taVNS may help regulate autonomic nervous system functions related to sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of transcutaneous auricular vagus nerve stimulation on nocturnal autonomic nervous function in primary insomnia patients]. Zhao, YN., Li, SY., Li, SX., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Vagus nerve stimulation is an effective treatment for drug-resistant epilepsy, but it can have side effects such as cough, voice changes, and, in rare cases, obstructive sleep apnea and arrhythmia.

Guidelines have been developed to help clinicians manage patients with vagus nerve stimulation devices during surgery and critical care, emphasizing the importance of deactivating the device before anesthesia and consulting neurology during critical illness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of vagus nerve stimulation therapy in the peri-operative period: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists. Broderick, L., Tuohy, G., Solymos, O., et al.[2023]

In the PRESTO trial involving 248 patients with episodic migraine, non-invasive vagus nerve stimulation (nVNS) significantly increased the likelihood of achieving pain relief at 60 and 120 minutes post-treatment compared to a sham device, demonstrating its efficacy as an acute treatment.

The safety profile of nVNS was strong, with low incidence of adverse events and no serious adverse events reported, suggesting it is a reliable option for migraine treatment that can be used alongside traditional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial. Martelletti, P., Barbanti, P., Grazzi, L., et al.[2020]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

In a study of 24 children undergoing intermittent vagal nerve stimulation over a total of 61 patient years, 15 adverse events were reported, with 13 likely related to the device, indicating a need for careful monitoring during treatment.

Despite the occurrence of adverse events, vagal nerve stimulation was generally well tolerated, and unlike standard drug therapies, these events did not typically require stopping the treatment, although they sometimes led to unexpected surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in children receiving intermittent left vagal nerve stimulation. Murphy, JV., Hornig, GW., Schallert, GS., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599790/

Transcutaneous Vagus Nerve Stimulation Could Improve the ... The primary outcome assessed was the effective rate of treatment, defined as ≥50% reduction in the Pittsburgh Sleep Index Scale (PSQI) score after treatment.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2828072

Transcutaneous Auricular Vagus Nerve Stimulation for ... Compared with sham taVNS group, 8 weeks taVNS treatment significantly improved sleep quality, reduced insomnia severity, and alleviated accompanying symptoms of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945725002540

Transcutaneous auricular vagus nerve stimulation (taVNS ... taVNS significantly improved sleep quality, insomnia severity, and overall quality of life compared to sham. These findings establish taVNS as a safe and ...

4. esmed.org esmed.org/MRA/mra/article/view/6132

Role of Effective Noninvasive Vagal Stimulation on sleep ... In this review we are exploring the role of noninvasive vagal nerve stimulation as an add on therapeutic tool in insomnia patients.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04021537

NCT04021537 | Non-invasive Nerve Stimulation and Sleep Transcutaneous Vagal Nerve Stimulation Improvement of Sleep Quality in Veterans With PTSD With or Without History of Mild TBI. Conditions. PTSD. PTSD. PTSD.

6. mayoclinic.org mayoclinic.org/tests-procedures/vagus-nerve-stimulation/about/pac-20384565

Vagus nerve stimulation Having a vagus nerve stimulator put into the body is safe for most people. But it does have some risks. These come both from the surgery to ...

7. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-015-0582-9

Cervical non-invasive vagus nerve stimulation (nVNS) for ... In this study, treatment with nVNS was safe and provided clinically meaningful decreases in the frequency and intensity of migraine attacks in patients with ...