Alcohol Use DisorderNCT06399653
Non-invasive Vagal Nerve Stimulation as Novel Treatment to Improve Functional Outcomes in Veterans With Alcohol Use Disorder
A study testing Cervical transcutaneous vagus nerve stimulation (active comparator) in people with Alcohol Use Disorder, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Cervical transcutaneous vagus nerve stimulation (active comparator)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2025to 31 Aug 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161-0002
Ruth Klaming, PhD, 858-642-3538, Ruth.Miller@va.gov
Ruth Klaming, PhD
About this study
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.
Read the detailed description
Alcohol use disorder (AUD) is a serious mental health disorder that affects more than 40% of US military Veterans, presenting a major burden to this population and to the VA Healthcare System. Relapse rates of AUD are extremely high; over half of Veterans who complete treatment, relapse within 6 months, highlighting the need for improved treatments or different treatment targets. Long-term excessive drinking results in homeostatic dysregulation due to changes in the central and autonomic nervous system, which manifests in psychological and physical distress during abstinence and results in the urge to drink to relieve these symptoms. These symptoms, which can be equated to withdrawal, lead to continued harmful drinking and relapse, and are associated with significant functional impairment and reduced quality of life.
Current AUD treatments do not effectively mitigate this homeostatic dysregulation and have risks and side effects as well as other limitations. The investigators propose the vagus nerve, which is the main nerve of the parasympathetic branch of the autonomic nervous system and plays an important role in maintaining and restoring physiological homeostasis, as a novel treatment target for AUD. Noninvasive stimulation of the vagus nerve (nVNS) has been shown to alleviate anxiety, depression, and pain. The investigators hypothesize that nVNS can restore homeostasis and reduce withdrawal-related distress and craving, and consequently improve functional outcomes and quality of life in Veterans with AUD.
The goal of this study is to assess treatment efficacy and mechanism of action. The proposed study will include 80 Veterans with current AUD, who will be randomized to receive nVNS or sham stimulation prior to performing a well-validated heat pain task designed to assess neural and physiological correlates of distress. Subjects will then self-administer nVNS/sham at home twice a day for 7 days and return for a follow-up visit, during which all study components will be repeated. Behavioral assessments of psychological and physiological distress, craving, and functional outcomes will be administered at baseline and post-treatment, as well as at a 1-month follow-up visit.
- Conditions
- Alcohol Use Disorder
- Being tested
- Cervical transcutaneous vagus nerve stimulation (active comparator), Cervical transcutaneous vagus nerve stimulation (sham comparator)
- Keywords
- alcohol use disorder, neuromodulation, neuroimaging, withdrawal, anxiety, autonomic nervous system
- Medical subject headings
- Alcoholism, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cervical transcutaneous vagus nerve stimulation (active comparator)Device
Also called gammaCore
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.
Cervical transcutaneous vagus nerve stimulation (sham comparator)Device
Also called sham
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.
| Study group | Role | What they receive |
|---|---|---|
| Active cervical transcutaneous vagus nerve stimulation | Active comparator | 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. Receives: Device: Cervical transcutaneous vagus nerve stimulation (active comparator) |
| Sham cervical transcutaneous vagus nerve stimulation | Placebo comparator | 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. Receives: Device: Cervical transcutaneous vagus nerve stimulation (sham comparator) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Anxiety Rating Scale (HAM-A)
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).
Measured: Baseline to week 1 and 1 month post baseline of 2x daily intervention
Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)
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)
Measured: Baseline to week 1 and 1 month post baseline of 2x daily intervention
Alcohol Urge Questionnaire (AUQ)
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.
Measured: Baseline to week 1 and 1 month post baseline of 2x daily intervention
WHO Quality of Life assessment (WHOQOL-BREF)
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.
Measured: Baseline to week 1 and 1 month post baseline of 2x daily intervention
Secondary outcomes (1)
Neural response to heat pain fMRI task
During this task, participants receive brief thermal stimuli (experienced temperature ranging from warm to hot) applied to the leg via a thermode. Neural activation will be measured using percent signal change with higher scores indicating greater activation.
Measured: Baseline to week 1 of 2x daily intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2024
- Study start1 Jan 2025
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly assigned to receive either active or placebo stimulation, and will receive identical instructions on use of the device. Participants will remain in the same condition assigned at baseline and will be instructed to self-administer nVNS/sham at home for 7 days (2 mins bilaterally, 2x per day) and return for a follow-up visit. Stimulation will be administered by the examiner during a functional MRI scan during the baseline and the follow-up visit.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Ruth Klaming, PhD, Principal investigator, VA San Diego Healthcare System, San Diego, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06399653
- Sponsor's protocol ID
- N4777-M
- Status last verified
- Mar 2026
- First submitted
- 30 Apr 2024
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Vagal Nerve Stimulation as Novel Treatment to Improve Functional Outcomes in Veterans With Alcohol Use Disorder
- ClinicalTrials.gov ID
- NCT06399653
- Acronym / sponsor ID
- N4777-M
- Conditions
- Alcohol Use Disorder
- Keywords
- alcohol use disorder, neuromodulation, neuroimaging, withdrawal, anxiety, autonomic nervous system
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Jan 2025 (actual)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 6 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Alcohol use disorder (AUD) is a serious mental health disorder that affects more than 40% of US military Veterans, presenting a major burden to this population and to the VA Healthcare System. Relapse rates of AUD are extremely high; over half of Veterans who complete treatment, relapse within 6 months, highlighting the need for improved treatments or different treatment targets. Long-term excessive drinking results in homeostatic dysregulation due to changes in the central and autonomic nervous system, which manifests in psychological and physical distress during abstinence and results in the urge to drink to relieve these symptoms. These symptoms, which can be equated to withdrawal, lead to continued harmful drinking and relapse, and are associated with significant functional impairment and reduced quality of life.
Current AUD treatments do not effectively mitigate this homeostatic dysregulation and have risks and side effects as well as other limitations. The investigators propose the vagus nerve, which is the main nerve of the parasympathetic branch of the autonomic nervous system and plays an important role in maintaining and restoring physiological homeostasis, as a novel treatment target for AUD. Noninvasive stimulation of the vagus nerve (nVNS) has been shown to alleviate anxiety, depression, and pain. The investigators hypothesize that nVNS can restore homeostasis and reduce withdrawal-related distress and craving, and consequently improve functional outcomes and quality of life in Veterans with AUD.
The goal of this study is to assess treatment efficacy and mechanism of action. The proposed study will include 80 Veterans with current AUD, who will be randomized to receive nVNS or sham stimulation prior to performing a well-validated heat pain task designed to assess neural and physiological correlates of distress. Subjects will then self-administer nVNS/sham at home twice a day for 7 days and return for a follow-up visit, during which all study components will be repeated. Behavioral assessments of psychological and physiological distress, craving, and functional outcomes will be administered at baseline and post-treatment, as well as at a 1-month follow-up visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomly assigned to receive either active or placebo stimulation, and will receive identical instructions on use of the device. Participants will remain in the same condition assigned at baseline and will be instructed to self-administer nVNS/sham at home for 7 days (2 mins bilaterally, 2x per day) and return for a follow-up visit. Stimulation will be administered by the examiner during a functional MRI scan during the baseline and the follow-up visit.
| Arm | Type | Receives |
|---|---|---|
| Active cervical transcutaneous vagus nerve stimulation | Active comparator | Device: Cervical transcutaneous vagus nerve stimulation (active comparator)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. |
| Sham cervical transcutaneous vagus nerve stimulation | Placebo comparator | Device: Cervical transcutaneous vagus nerve stimulation (sham comparator)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 may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cervical transcutaneous vagus nerve stimulation (active comparator)Also: gammaCoreActive 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 | Active cervical transcutaneous vagus nerve stimulation |
| Cervical transcutaneous vagus nerve stimulation (sham comparator)Also: shamSham 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. | Device | Sham cervical transcutaneous vagus nerve stimulation |
Primary outcome
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.
1 secondary outcome
Neural response to heat pain fMRI task
Time frame: Baseline to week 1 of 2x daily intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ruth Klaming, PhD principal investigator
VA San Diego Healthcare System, San Diego, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cervical transcutaneous vagus nerve stimulation (active comparator) in people with Alcohol Use Disorder, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ruth Klaming, PhD ((858) 642-3538, Ruth.Miller@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Anxiety Rating Scale (HAM-A) (time frame: Baseline to week 1 and 1 month post baseline of 2x daily intervention). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.