Vagal Nerve Stimulation for Alcoholism

Overseen By Ruth Klaming, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Opioids, Benzodiazepines

Disqualifiers: Severe psychiatric disorder, Neurological disorder, Uncontrolled medical illness, others

Compensation: Varies

Number of Visits: 3

Duration: 1 week

80 Participants Needed

Trial Summary

What is the purpose of this trial?

Alcohol use disorder (AUD) is a major health concern amongst Veterans as it causes functional impairments and decreased quality of life. Current AUD treatments show limited effectiveness in reducing withdrawal-related psychological and physical distress, which drives the urge to drink to relieve these symptoms. The investigators propose the vagus nerve, which is the primary nerve of the "rest and digest" branch of the autonomic nervous system via its bidirectional connections between the brain and the body, as a novel treatment target for AUD. The goal of this study is to assess treatment efficacy and mechanism of action. Noninvasive neuromodulation technologies offer the possibility for innovative, low risk treatments to support the rehabilitation and community reintegration of Veterans with AUD.

Will I have to stop taking my current medications?

The trial requires that participants have at least 2 weeks of stable medication use for alcohol use disorder (AUD) before starting the study. If you are currently taking opioids or benzodiazepines, you will not be eligible to participate.

What data supports the effectiveness of the treatment Cervical transcutaneous vagus nerve stimulation for alcoholism?

Research on similar treatments, like auricular transcutaneous vagus nerve stimulation, shows it can improve symptoms like depression and sleep quality in alcohol-dependent patients. Additionally, vagus nerve stimulation has shown benefits in treatment-resistant depression, suggesting potential for improving mood and cognitive control in alcoholism. ^{1 2 3 4 5}

Is vagus nerve stimulation safe for humans?

Vagus nerve stimulation, including non-invasive methods like transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe with mild and temporary side effects such as ear pain, headache, and tingling. Serious side effects are rare, and non-invasive systems improve safety by avoiding surgery. ^{1 6 7 8 9}

How is cervical transcutaneous vagus nerve stimulation different from other treatments for alcoholism?

Cervical transcutaneous vagus nerve stimulation is unique because it is a non-invasive treatment that stimulates the vagus nerve through the skin, potentially enhancing cognitive control processes crucial for managing alcohol intake. Unlike traditional treatments, it does not require surgery and can be integrated into daily life, offering a novel approach for those who do not respond well to existing therapies. ^{1 10 11 12 13}

Research Team

Ruth Klaming, PhD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Eligibility Criteria

This trial is for veterans with Alcohol Use Disorder (AUD) who are seeking new treatments to improve their quality of life and reduce the urge to drink. Specific eligibility criteria details were not provided, so interested individuals should contact the study organizers for more information.

Inclusion Criteria

Meet current DSM-5 diagnosis of moderate or severe AUD with at least one functional disability due to alcohol use, current alcohol craving, and current heavy drinking

Able to forgo consumption of alcohol for 12-24 hours without any serious discomfort or complications

Capable of complying with study schedule, procedures, and speaks English

Exclusion Criteria

In case it is determined by the investigator during the course of the study, that a subject needs a higher level or care, study participation will be discontinued, and the subject will be excluded from the study.

I am currently taking opioids or benzodiazepines.

Currently or recently (within last 90 days) enrolled in abstinence-based treatment program

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham transcutaneous vagus nerve stimulation, administered once during each study visit and self-administered twice a day for 7 days

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at baseline, post-treatment, and at a 1-month follow-up visit

1 month

1 visit (in-person)

Treatment Details

Interventions

• Cervical transcutaneous vagus nerve stimulation

Trial Overview The trial is testing a non-invasive treatment called cervical transcutaneous vagus nerve stimulation. Participants will be randomly assigned to receive either the active treatment or a sham (placebo) version to compare outcomes in managing AUD symptoms.

Participant Groups

Group I: Active cervical transcutaneous vagus nerve stimulation Active Control 1 Intervention

Participants will be assigned to active transcutaneous vagus nerve stimulation, received once during each of the study visits and self-administered twice a day for a week.

Group II: Sham cervical transcutaneous vagus nerve stimulation Placebo Group 1 Intervention

Participants will be assigned to sham transcutaneous vagus nerve stimulation, received once during each of the study visits and self-administered twice a day for a week.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Auricular transcutaneous vagus nerve stimulation (atVNS) may serve as an effective add-on treatment for alcohol use disorder (AUD) by directly stimulating brain areas that regulate neurotransmitters affected by alcohol, potentially improving cognitive control and aiding in maintaining abstinence.

AtVNS can be easily integrated into daily life as it is a noninvasive technique that can be worn like an earpiece, making it a convenient option for patients who struggle with traditional treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular transcutaneous vagus nerve stimulation for alcohol use disorder: A chance to improve treatment? Konjusha, A., Colzato, L., Ghin, F., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) shows potential as a treatment for disorders of consciousness, particularly in patients with a minimally conscious state (MCS), as it significantly alters brain activity measured by EEG.

In patients with MCS, taVNS led to notable changes in both delta and beta brain wave energy across multiple regions, suggesting it may enhance brain connectivity and promote awakening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. Yifei, W., Yi, Y., Yu, W., et al.[2023]

In a study of 6 patients with treatment-resistant depression, vagus nerve stimulation (VNS) showed significant improvements in depression scores after both 3 months and 12 months, indicating its potential as an effective treatment option.

The patients tolerated VNS well, suggesting it is a safe intervention, but further controlled studies are needed to confirm these promising results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in treatment-resistant depression: acute and follow-up results of an italian case series. Dell'Osso, B., Oldani, L., Palazzo, MC., et al.[2013]

Transcutaneous cervical vagus nerve stimulation (tcVNS) significantly increased motor cortex excitability in healthy adults, as evidenced by a notable increase in motor-evoked potential (MEP) amplitude after real stimulation compared to sham stimulation.

The study involved 28 healthy participants and demonstrated that real tcVNS not only increased MEP amplitude but also decreased MEP latency, indicating a faster response time in the motor cortex, while no significant changes were observed in the resting motor threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous cervical vagus nerve stimulation improved motor cortex excitability in healthy adults: a randomized, single-blind, self-crossover design study. Wang, MX., Wumiti, A., Zhang, YW., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved depression symptoms and sleep quality in 114 patients with alcohol dependence, as indicated by lower scores on the Self-Rating Depression Scale and Pittsburgh Sleep Quality Index compared to a control group.

The treatment with taVNS also led to a significant increase in plasma brain-derived neurotrophic factor (BDNF) levels, suggesting a potential mechanism for its efficacy in alleviating protracted alcohol withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Protracted Alcohol Withdrawal Symptoms in Male Alcohol-Dependent Patients. Wang, YM., Xu, YY., Zhai, Y., et al.[2021]

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 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]

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]

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]

A systematic review of 261 studies revealed significant confusion in the nomenclature for transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN), with 67 full and 27 abbreviated terms identified, highlighting the need for standardization.

The most commonly used terms were 'transcutaneous vagus nerve stimulation' and 'tVNS', but there was no consistent one-to-one relationship between full and abbreviated names, indicating a lack of uniformity in terminology across different research teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. Wang, Y., Li, L., Li, S., et al.[2023]

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 vagus nerve stimulation (tVNS) is a non-invasive and less expensive alternative to invasive vagus nerve stimulation (VNS), which is used to treat conditions like epilepsy and depression, but requires further research to optimize stimulation sites and parameters.

tVNS has the potential to activate various brain areas and may be effective for a wide range of conditions, including medication-refractory epilepsy, depression, migraines, and more, suggesting it could become a standard treatment for enhancing autonomic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation - A brief introduction and overview. Hilz, MJ.[2022]

In a study involving 17 healthy adults, transcutaneous auricular vagus nerve stimulation (taVNS) at the left tragus significantly increased brain activity in areas associated with the vagal pathway, indicating its potential efficacy in neuromodulation.

Compared to control stimulation at the earlobe, tragus stimulation resulted in greater activation in key brain regions, suggesting that taVNS could be a promising therapeutic approach for influencing brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. Badran, BW., Dowdle, LT., Mithoefer, OJ., et al.[2020]

References

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

Auricular transcutaneous vagus nerve stimulation for alcohol use disorder: A chance to improve treatment? [2022]

2. China pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. [2023]

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

Vagus nerve stimulation in treatment-resistant depression: acute and follow-up results of an italian case series. [2013]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous cervical vagus nerve stimulation improved motor cortex excitability in healthy adults: a randomized, single-blind, self-crossover design study. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Protracted Alcohol Withdrawal Symptoms in Male Alcohol-Dependent Patients. [2021]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

9. 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]

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

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. [2023]

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

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

12. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation - A brief introduction and overview. [2022]

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

Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. [2020]