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

50 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Non-invasive Vagus Nerve Stimulation for improving sleep?

Research on vagus nerve stimulation (VNS) in epilepsy patients shows it can affect sleep by improving alertness and reducing rapid eye movement (REM) sleep, which might suggest potential benefits for sleep quality. However, VNS can also cause sleep disturbances like sleep apnea, indicating mixed effects on sleep. ^{1 2 3 4 5}

Is vagus nerve stimulation safe for humans?

Vagus nerve stimulation (VNS), including non-invasive methods, is generally considered safe for humans. Common mild side effects include voice changes, tingling, and ear pain, while serious issues are rare. Non-invasive VNS is safer than surgical options, as it avoids surgery-related risks. ^{6 7 8 9 10}

How does vagus nerve stimulation differ from other sleep treatments?

Vagus nerve stimulation (VNS) for sleep is unique because it uses a non-invasive method called transcutaneous auricular vagus nerve stimulation (taVNS), which involves stimulating the vagus nerve through the skin of the ear. This approach is different from traditional sleep treatments as it is non-surgical, portable, and can be administered at home, offering a novel way to potentially improve sleep quality without medication. ^{2 11 12 13 14}

What is the purpose of this trial?

Participants will be chosen at random to receive a 30-minute stimulation of a specialized nerve (called a vagus nerve). 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. Participants will visit the lab on 2 occasions (one with a stimulating device and one without), 3 weeks apart for detailed instruction on setting up the ear stimulation and sleep kit in their home. Researchers will compare the sleep results from a PSG sleep device from the 2 sessions to determine the effect, if any on sleep.

Eligibility Criteria

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

I have a history of heart, lung, kidney, or liver disease.

Pregnancy or lactation due to the location of the sleep devices

Presence of any other condition that, in the opinion of the PI, makes the individual unsuitable for participation

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Chronic vagus nerve stimulation improves alertness and reduces rapid eye movement sleep in patients affected by refractory epilepsy. [2019]

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

Sleep apnea and excessive daytime somnolence induced by vagal nerve stimulation. [2019]

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

Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients. [2022]

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

The effects of vagus nerve stimulation on sleep EEG in depression: a preliminary report. [2019]

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

Investigating the Effect of Short Term Responsive VNS Therapy on Sleep Quality Using Automatic Sleep Staging. [2020]

6. England 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. [2023]

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

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

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

Adverse events in children receiving intermittent left vagal nerve stimulation. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

10. England 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. [2020]

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

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

12. China pubmed.ncbi.nlm.nih.gov

[Effect of transcutaneous auricular vagus nerve stimulation on nocturnal autonomic nervous function in primary insomnia patients]. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

A two-week course of transcutaneous vagal nerve stimulation improves global sleep: Findings from a randomised trial in community-dwelling adults. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Chronic stimulation of the cat vagus nerve: effect on sleep and behavior. [2019]