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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help Veterans with alcohol use disorder (AUD) using a device that stimulates the vagus nerve, which controls stress and relaxation. The goal is to determine if this approach can reduce the urge to drink by easing withdrawal symptoms. Participants will use either the active device or a sham (inactive) version for comparison. Veterans struggling with heavy drinking and cravings, who can abstain from alcohol for a short period, might be suitable candidates. As an unphased trial, this study offers Veterans a unique opportunity to explore innovative treatments for 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 prior data suggests that this device is safe for treating alcohol use disorder?

Research has shown that cervical transcutaneous vagus nerve stimulation, which uses gentle electrical pulses on the skin, is generally well-tolerated. In studies, most participants experienced only mild side effects, such as slight discomfort or tingling at the application site. No serious side effects were reported. This treatment has also been studied for other conditions, like opioid withdrawal, with similar safety outcomes. It is considered low risk, making it a promising option for those exploring new treatments for alcohol use disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about cervical transcutaneous vagus nerve stimulation (tVNS) for alcoholism because it offers a non-invasive, innovative approach compared to traditional treatments like medications or behavioral therapies. Unlike medications that alter brain chemistry, tVNS stimulates the vagus nerve through the skin, potentially reducing alcohol cravings and improving mood. This method targets the nervous system directly, offering a new pathway that could complement existing treatments, and is easy to self-administer, which may increase adherence and accessibility for patients.

What evidence suggests that cervical transcutaneous vagus nerve stimulation is effective for alcohol use disorder?

This trial will compare active cervical transcutaneous vagus nerve stimulation with a sham version to evaluate its effectiveness in managing symptoms of alcohol use disorder (AUD). Research has shown that stimulating the vagus nerve through the skin can help reduce the distress people with AUD feel when they stop drinking, which often leads them to drink again to feel better. Studies have found that this nerve stimulation can lift mood and lessen anxiety and depression, common in people with AUD. It has also helped with conditions like treatment-resistant depression, suggesting it might improve mood and mental control. Early results are promising, indicating this method could be a safe and new way to manage AUD symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

Ruth Klaming, PhD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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 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]

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]

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]

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]

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]

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]

Citations

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Noninvasive Vagus Nerve Stimulation Reduces ... Noninvasive Vagus Nerve Stimulation Reduces Withdrawal-Related Affective Distress and Improves Functional Outcomes in Alcohol Use Disorder: A ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05226130

Non-invasive Vagal Nerve Stimulation in Alcohol Use ... Current treatment options for AUD show limited effectiveness, which is exemplified by high relapse rates. Chronic heavy drinking results in psychological and ...

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Transcutaneous cervical vagus nerve stimulation reduces ... Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder.

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06399653

Non-invasive Vagal Nerve Stimulation as Novel Treatment ... Noninvasive stimulation of the vagus nerve (nVNS) has been shown to alleviate anxiety, depression, and pain. The investigators hypothesize that ...

5. withpower.com withpower.com/trial/phase-2-and-3-alcohol-drinking-6-2024-41e57

Vagal Nerve Stimulation for Alcoholism Additionally, vagus nerve stimulation has shown benefits in treatment-resistant depression, suggesting potential for improving mood and cognitive control in ...

6. nature.com nature.com/articles/s41598-022-25864-1

Safety of transcutaneous auricular vagus nerve stimulation ... Although the general impression is that taVNS is a safe technique with only mild and transient adverse effects (AEs), human data on safety and ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/adb.13202

Auricular transcutaneous vagus nerve stimulation for ... Here, we discuss the potential use of auricular transcutaneous vagus nerve stimulation (atVNS) as an ADD-ON intervention in AUD.