Non-invasive Vagal Nerve Stimulation as Novel Treatment to Improve Functional Outcomes in Veterans With Alcohol Use Disorder

NCT06399653 | Recruiting FDA Device

• 1 other identifier: N4777-M
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Alcohol Use Disorder

Keywords

alcohol use disorder; neuromodulation; neuroimaging; withdrawal; anxiety; autonomic nervous system

Outcome Measures

Primary Outcomes (4)

• 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).

  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)

  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.

  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.

  Baseline to week 1 and 1 month post baseline of 2x daily intervention

Secondary Outcomes (1)

• Neural response to heat pain fMRI task

  Baseline to week 1 of 2x daily intervention

Other Outcomes (3)

• Physiological response to heat pain fMRI task

  Baseline to week 1 of 2x daily intervention

• The Drinker Inventory of Consequences (DrInC)

  Baseline to week 1 and 1 month post baseline of 2x daily intervention

• Substance Use Recovery Evaluator (SURE)

  Baseline to week 1 and 1 month post baseline of 2x daily intervention

Study Arms (2)

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.

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.

Device: Cervical transcutaneous vagus nerve stimulation (sham comparator)

Interventions

Cervical transcutaneous vagus nerve stimulation (active comparator) DEVICE

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.

Also known as: gammaCore

Active cervical transcutaneous vagus nerve stimulation

Cervical transcutaneous vagus nerve stimulation (sham comparator) DEVICE

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.

Also known as: sham

Sham cervical transcutaneous vagus nerve stimulation

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

RECRUITING

MeSH Terms

Conditions

Alcoholism; Anxiety Disorders

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Ruth Klaming, PhD

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruth Klaming, PhD

CONTACT

(858) 642-3538; Ruth.Miller@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Devices will be masked to ensure both the research team involved in data collection and participants are blinded (double-blind study design). An unblinded member of the research team, not involved in data collection and subject contact, will assign randomization, provide device identification number, and keep the key linking condition to identification numbers.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: May 6, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2029
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)