Vagal Nerve Stimulation for Alcoholism
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: VA Office of Research and Development
Must not be taking: Opioids, Benzodiazepines
Disqualifiers: Severe psychiatric disorder, Neurological disorder, Uncontrolled medical illness, others
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.
12345Is 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.
16789How 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.
110111213Eligibility 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
+3 more
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
+11 more
Trial 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)
Participant Groups
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.
2Treatment groups
Active Control
Placebo Group
Group I: Active cervical transcutaneous vagus nerve stimulationActive Control1 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 stimulationPlacebo Group1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
VA San Diego Healthcare System, San Diego, CASan Diego, CA
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Who Is Running the Clinical Trial?
VA Office of Research and DevelopmentLead Sponsor
References
Auricular transcutaneous vagus nerve stimulation for alcohol use disorder: A chance to improve treatment? [2022]Alcohol use disorder (AUD) is a relapsing-remitting condition characterized by excessive and/or continued alcohol consumption despite harmful consequences. New adjuvant tools, such as noninvasive brain stimulation techniques, might be helpful additions to conventional treatment approaches or even provide an alternative option for patients who fail to respond adequately to other treatment options. Here, we discuss the potential use of auricular transcutaneous vagus nerve stimulation (atVNS) as an ADD-ON intervention in AUD. Compared with other techniques, atVNS has the advantage of directly stimulating nuclei that synthesize GABA and catecholamines, both of which are functionally altered by alcohol intake in AUD patients. Pharmacological options targeting those neurotransmitters are widely available, but have relatively limited beneficial effects on cognition, even though restoring normal cognitive functioning, especially cognitive control, is key to maintaining abstinence. Against this background, atVNS could be a particularly useful add-on because there is substantial meta-analytic evidence based on studies in healthy individuals that atVNS can enhance cognitive control processes that are crucial to regaining control over drug intake. We discuss essential future research on using atVNS as an ADD-ON intervention in AUD to enhance clinical and cognitive outcomes by providing a translational application. Given that this novel technique can be worn like an earpiece and can be employed without medical supervision/outside the clinical settings, atVNS could be well integratable into the daily life of the patients, where the task of regaining control over drug intake is most challenging.
Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. [2023]To evaluate the clinical effect of transcutaneous auricular vagus nerve nerve stimulation (taVNS) on disorders of consciousness (DOC) patients with Coma Recovery Scale-Revised (CRS-R) and cerebral cortex activity by electroencephalogram (EEG) detection.
Vagus nerve stimulation in treatment-resistant depression: acute and follow-up results of an italian case series. [2013]The present study evaluated short- and long-term efficacy and tolerability of augmentative vagus nerve stimulation (VNS) in a group of patients with treatment-resistant depression (N = 6). A statistically significant improvement in the Hamilton Depression Rating Scale (HDRS21) and Montgomery-Asberg Depression Rating Scale after 3 months (P = 0.039 and P = 0.05, respectively) was found in comparison with baseline (VNS implant). After 12 months, a statistically significant improvement was observed in the Hamilton Depression Rating Scale (HDRS21), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impression (P = 0.01, P = 0.005, and P = 0.001, respectively). Patients showed an overall favorable tolerability. Present data support VNS short- and long-term efficacy and tolerability in a small group of patients with treatment-resistant depression. Further controlled investigation is necessary to confirm the present open findings.
Transcutaneous cervical vagus nerve stimulation improved motor cortex excitability in healthy adults: a randomized, single-blind, self-crossover design study. [2023]To investigate the effect of transcutaneous cervical vagus nerve stimulation (tcVNS) on motor cortex excitability in healthy adults.
Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Protracted Alcohol Withdrawal Symptoms in Male Alcohol-Dependent Patients. [2021]Protracted alcohol withdrawal symptoms (PAWS), characterized by the presence of substance-specific signs and symptoms (including anxiety, irritability, mood instability, insomnia, and cravings), make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. The goal of this study was to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on PAWS and plasma brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin levels in patients with alcohol dependency. A total of 114 patients with alcohol dependence were randomly divided into two groups: the treatment group and the control group. The patients in the treatment group were treated with taVNS of the bilateral auricular concha using an ear vagus nerve stimulator. The Pennsylvania Alcohol Craving Scale was used to evaluate the extent of craving for alcohol. The Self-Rating Anxiety Scale and Self-Rating Depression Scale (SDS) were used to evaluate the extent of anxiety and depression symptoms, respectively. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Enzyme-linked immunosorbent assay was used to measure plasma BDNF, IL-6, TNF-α, and leptin levels. The results showed that the SDS and PSQI scores were significantly lower in the treatment group than in the control group. Moreover, compared with the control group, the average BDNF levels in the treatment group were significantly increased. These results suggest that taVNS could improve the depression symptoms and sleep quality in alcohol-dependent patients after withdrawal, which might be related to the upregulation of plasma BDNF levels.
Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.
Adverse events in children receiving intermittent left vagal nerve stimulation. [2019]The purpose of this study was to determine the frequency of unexpected events during intermittent vagal nerve stimulation in 24 patients stimulated for a total of 61 patient years. The charts of 24 children undergoing periodic stimulation of the left vagal nerve on research protocols were reviewed to determine the nature and frequency of adverse events and the total length of time they were stimulated. Fifteen adverse events were discovered in 12 patients. Thirteen were likely related to the device, and four other events might have been related. Two of these resulted in voluntary termination of vagal nerve stimulation, and the rest were treatable. Vagal nerve stimulation was tolerated in this series of patients. As opposed to the more standard drug therapies, adverse events during vagal nerve stimulation do not necessitate termination of therapy, but these events frequently lead to unforeseen surgery under general anesthesia.
Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.
Management of vagus nerve stimulation therapy in the peri-operative period: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists. [2023]Vagus nerve stimulation is a well-established treatment option for patients with drug-resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri-operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services.
Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. [2023]After 20 years of development, there is confusion in the nomenclature of transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN). We performed a systematic review of transcutaneous stimulation of ABVN in nomenclature.
Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus nerve stimulation (taVNS). Unlike cervically-implanted VNS, taVNS is an inexpensive and non-surgical method used to modulate the vagus system. taVNS is appealing as it allows for rapid translation of basic VNS research and serves as a safe, inexpensive, and portable neurostimulation system for the future treatment of central and peripheral disease. The background and rationale for taVNS is described, along with electrical and parametric considerations, proper ear targeting and attachment of stimulation electrodes, individual dosing via determination of perception threshold (PT), and safe administration of taVNS.
Transcutaneous vagus nerve stimulation - A brief introduction and overview. [2022]Invasive cervical vagus nerve stimulation (VNS) is approved for the treatment of epilepsies, depression, obesity, and for stroke-rehabilitation. The procedure requires surgery, has side-effects, is expensive and not readily available. Consequently, transcutaneous VNS (tVNS) has been developed 20 years ago as non-invasive, less expensive, and easily applicable alternative. Since the vagus nerve reaches the skin at the outer acoustic canal and ear, and reflex-responses such as the ear-cough-reflex or the auriculo-cardiac reflex have been observed upon auricular stimulation, the ear seems well suited for tVNS. However, several sensory nerves with variable fiber-density and significant overlap innervate the outer ear: the auricular branch of the vagus nerve (ABVN), the auriculotemporal nerve, greater auricular nerve, and to some extent the lesser occipital nerve. VNS requires activation of Aβ-fibers which are far less present in the ABVN than the cervical vagus nerve. Thus, optimal stimulation sites and parameters, and tVNS-algorithms need to be further explored. Unravelling central pathways and structures that mediate tVNS-effects is another challenge. tVNS impulses reach the nucleus of the solitary tract and activate the locus-coeruleus-norepinephrine system. However, many more brain areas are activated or deactivated upon VNS, including structures of the central autonomic network and the limbic system. Still, the realm of therapeutic tVNS applications grows rapidly and includes medication-refractory epilepsies, depressive mood disorders, headaches including migraine, pain, heart failure, gastrointestinal inflammatory diseases and many more. tVNS might become a standard tool to enhance autonomic balance and function in various autonomic, neurological, psychiatric, rheumatologic, as well as other diseases.
Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. [2020]Electrical stimulation of the auricular branch of the vagus nerve (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with inconsistent findings due to variability in stimulation targets and parameters.