NCT06399653 · VA Office of Research and Development
Non-invasive Vagal Nerve Stimulation as Novel Treatment to Improve Functional Outcomes in Veterans With Alcohol Use Disorder
What this study is about
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.
View original scientific description
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.
Interventions
DEVICE
Cervical transcutaneous vagus nerve stimulation (active comparator)
Active nVNS produces low-voltage electrical signal that generates sensations on the skin on upper anterior cervical area (overlying carotid artery) and that stimulates the vagus nerve.
DEVICE
Cervical transcutaneous vagus nerve stimulation (sham comparator)
Sham nVNS devices look identical to active devices and participants will undergo identical training for self-administration on upper anterior cervical area (overlying carotid artery). Sham devices do not stimulate the vagus nerve.
Primary outcome measures
Hamilton Anxiety Rating Scale (HAM-A)
Time frame: Baseline to week 1 and 1 month post baseline of 2x daily intervention
The HAM-A is a 14-item scale that assesses the presence and severity of psychological distress and negative emotional states. Completion takes 10 minutes. This instrument is widely used in clinical trials and alcohol studies and is sensitive to both nVNS and AUD treatment. Items are rated on a scale ranging from 0 (not present) to 4 (very severe).
Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)
Time frame: Baseline to week 1 and 1 month post baseline of 2x daily intervention
The Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) is a short form (5 min.) to assess symptoms of acute alcohol withdrawal and physical discomfort. The CIWA-Ar includes 8 items, 7 of which are rated from 1 to 7 (higher score indicating higher severity) and 1 of which is rated from 0 to 4 (higher score indication less orientation to place/or person)
Alcohol Urge Questionnaire (AUQ)
Time frame: Baseline to week 1 and 1 month post baseline of 2x daily intervention
The Alcohol Urge Questionnaire (AUQ) is 8-item scale that measures cognitive preoccupation with alcohol on a 7-point rating scale ranging from "strongly disagree" to "strongly agree". Two items are reverse scored. Higher scores reflect greater craving.
WHO Quality of Life assessment (WHOQOL-BREF)
Time frame: Baseline to week 1 and 1 month post baseline of 2x daily intervention
The WHOQOL-BREF assesses quality of life across four domains (physical health, psychological, social relationships, and environment) with a total of 26 questions. The WHOQOL-BREF is a widely used instrument with strong psychometric properties.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Veterans between 21 and 65 years, any race or ethnicity.
- Meet current DSM-5 diagnosis of moderate or severe AUD (Structured Clinical Interview for DMS-5 (SCID) interview) with at least one functional disability due to alcohol use, current alcohol craving, and current heavy drinking (\>= 5 drinks (men) / \>= 4 drinks (women) on the same occasion, on 5 or more days in the past month) as defined by the Substance Abuse and Mental Health Services Administration (SAMHSA), and mild to moderate withdrawal symptoms during abstinence.
- 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.
- Able to provide voluntary written informed consent prior to initiation of visit 1.
- Able and willing to self-administer nVNS/sham stimulation as instructed for the duration of the study, and willing to commit to the return visit at the end of the study.
Exclusion criteria
- Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) score \>10 on the day of the scan (symptoms judged to be due to co-existing anxiety or headache disorders will not be counted toward the total).
- Recent history past 6 months) of severe complications due to alcohol withdrawal (alcohol withdrawal seizures, hallucinations/illusions, delirium tremens).
- Currently or recently (within last 90 days) enrolled in abstinence-based treatment program.
- Evidence of a maladaptive pattern of substance use or abuse other than alcohol one month prior to screening visit.
- Uncontrolled severe psychiatric disorder with psychotic symptoms or cognitive impairment. We will not exclude for PTSD.
- At risk for suicide requiring urgent higher-level care or homicide (based on the Columbia-Suicide Severity Rating Scale and follow-up clinical interview).
- History of neurological disorder that might be associated with cognitive dysfunction.
- History of head trauma involving loss of consciousness \>24 hours
- Clinically significant uncontrolled/unstable medical illness or clinically significant surgery within 1 month of the screening visit.
- MRI-related exclusion criteria: cardiac pacemaker, metal fragments in eyes/skin/body, aortic/aneurysm clips, heart-valve replacement, copper intrauterine device, shunt (ventricular or spinal), neuro/bio-stimulators, (for females) pregnant or nursing. Any implants will be reviewed for safety.
- Vagus nerve stimulation related criteria: active implantable medical device, metallic device implanted at or near the neck, carotid atherosclerosis (narrowing of arteries), cervical vagotomy, clinically significant hypertension, hypotension, bradycardia, or tachycardia, cardiac disease and atherosclerotic cardiovascular disease (severe carotid artery disease (e.g., history of transient ischemic attack (TIA) or stroke), congestive heart failure, severe coronary artery disease or recent myocardial infarction (within 5 years)).
- Pharmacotherapy for AUD: \>= 2 weeks stability is required to ensure a steady state of medication effects prior to nVNS administration.
- Currently taking opioids or benzodiazepines.
- 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.
Where
- San Diego, California
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 23, 2026 · Source of record for eligibility and locations