Non-invasive Vagal Nerve Stimulation in Alcohol Use Disorder

NCT05226130 | Completed Phase 1 Results FDA Device

• 1 other identifier: D3629-M
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Alcohol use disorder (AUD) is a major health concern amongst Veterans as it causes poor health, lost days at work, impaired psychosocial functioning, and decreased quality of life. Current treatment options for AUD show limited effectiveness, which is exemplified by high relapse rates. Chronic heavy drinking results in psychological and physical distress during abstinence, including anxiety, irritability, and general discomfort, which increases the urge to drink to relieve these symptoms. The hypothesis of this study is that noninvasive vagal nerve stimulation (nVNS) can modify the perception of such inner bodily sensations of distress, and consequently reduces the drive to drink for relief. The aim of this study is to establish feasibility and acceptability of applying nVNS as a rehabilitative treatment for AUD in Veterans. The study will also evaluate the effect of nVNS on functional outcomes, quality of life, distress, and craving, and if nVNS alters neural activation patterns in brain regions involved in the perception and awareness of distress and pain.

Conditions

Alcohol Use Disorder

Keywords

alcohol use; neuromodulation; neuroimaging; withdrawal; anxiety; quality of life

Outcome Measures

Primary Outcomes (5)

• Treatment Acceptability Questionnaire (TAQ)

  The Treatment Acceptability Questionnaire (TAQ) is a self-rating questionnaire used to assess acceptability of a treatment. The TAQ uses a 7-point rating scale ranging from 1 to 7, with lower scores reflecting lower acceptability and a midpoint of 4 indicating neutral acceptability. A rating above the midpoint of the TAQ (i.e., score between 5 and 7) is the established criterion for "acceptable to highly acceptable".

  Measure administered at study completion (i.e., 1 week after baseline)

• Measurement of Feasibility - Recruitment Goal (Data Reflects the Number of Participants Who Were Successfully Enrolled in the Study)

  Treatment feasibility will be evaluated by meeting the proposed recruitment goal of 16 Veterans within 12 months. This aim was measured as the number of study participants who signed the study consent form, completed at least the baseline study visit, and were included in the study analyses.

  Baseline

• Measurement of Feasibility - Treatment Adherence (Number of Times Subjects Self-administered nVNS/Sham Stimulation for 7 Days as Instructed)

  Treatment adherence will be assessed via a daily treatment completion log, and calculated by dividing the total number of times subjects were instructed to self-administer the nVNS/sham stimulation (2x/day for 7 days = 14 times) by the number of times the subjects actually self-administered the stimulation. Treatment feasibility will be evaluated by meeting \>75% treatment adherence during the 1-week interval.

  Baseline to week 1 of 2x daily intervention

• Measurement of Feasibility - Subject Retention (Number/Percentage of Subjects Who Return for a Follow-up Visit)

  Treatment feasibility will be evaluated by meeting \>75% subject retention at follow-up as measured by the number/percentage of subjects who return for a follow-up visit and complete primary outcome measures and return the device to the study team.

  Baseline to post treatment, up to 21 days post baseline

• Measurement of Feasibility - Serious Adverse Side Effects

  Treatment feasibility will be evaluated by no occurrence of serious adverse side effects (as documented in checklist/daily log, interview at study completion, or otherwise reported by the participant).

  Baseline to week 1 of 2x daily intervention

Secondary Outcomes (5)

• Substance Use Recovery Evaluator (SURE)

  Baseline to week 1 of 2x daily intervention

• WHO Quality of Life Assessment (WHOQOL-BREF) - Psychological Domain

  Baseline to week 1 of 2x daily intervention

• Beck Anxiety Inventory (BAI)

  Baseline to week 1 of 2x daily intervention

• PROMIS Pain Interference

  Baseline to week 1 of 2x daily intervention

• Alcohol Urge Questionnaire (AUQ)

  Baseline to week 1 of 2x daily intervention

Other Outcomes (1)

• Neural Response to Heat Pain Stimuli (Measured as Sum of BOLD Beta Coefficients Over Time in Arbitrary Units)

  Baseline to week 1 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.

Active cervical transcutaneous vagus nerve stimulation

Cervical transcutaneous vagus nerve stimulation (sham comparator) DEVICE

Sham nVNS produces low-voltage electrical signal that generates sensations on the skin on upper anterior cervical area (overlying carotid artery) and that does not stimulate the vagus nerve.

Sham cervical transcutaneous vagus nerve stimulation

Eligibility Criteria

• Age: 21 Years - 65 Years
• Gender Eligibility Details: Parent study does not enroll women (due to potential sex differences in inflammation-induced alterations of brain response as well as sex differences in prevalence of PTSD), this study will not enroll women either to allow for post-hoc group comparisons. If significant effects are demonstrated with this study, follow-up grant proposals will include females.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veteran
• Male subjects between 21 and 65 years of age
• Current DSM-5 diagnosis of AUD with at least one functional disability due to alcohol use, current alcohol craving, and current heavy drinking (\>4 drinks on any day or \>14 drinks per week)
• Able to forgo consumption of alcohol for 24 hours without any serious discomfort including nausea/vomiting, visual/auditory/tactile hallucinations, or non-essential tremor

You may not qualify if:

• Clinical Institute Withdrawal Assessment of Alcohol Scale (CiWA) score \>=9 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).
• 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.
• Severe mental illness, e.g., psychosis or bipolar disorder
• At risk for suicide or homicide
• 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: history of carotid endarterectomy, severe carotid artery disease (e.g., history of transient ischemic attack (TIA) or stroke\], congestive heart failure, cardiac arrhythmia, known severe coronary artery disease or recent myocardial infarction (within 5 years), history of seizure or syncope (within past year), prior neck surgery.

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

Location

MeSH Terms

Conditions

Alcoholism; Alcohol Drinking; Anxiety Disorders

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Ruth Klaming, PhD
• Organization: VA San Diego Healthcare System, San Diego, CA

rklaming@health.ucsd.edu

858-552-8585

Study Officials

• Ruth Klaming, PhD

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both the research team involved in data collection and subjects will be blinded (double-blind study design). Subjects will be randomly assigned to receive either active or sham stimulation. Devices will be marked with an identification number to mask treatment condition. An unblinded Co-Investigator, 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: Devices include a sham and an active noninvasive vagal nerve stimulator (nVNS). Devices are identical in appearance, and both produce reliable sensation on the skin when applied to the neck area (transcutaneous cervical stimulation). Stimulation duration is approximately 120 seconds for both sham and active devices. Subjects receive the same instructions to self-administer stimulation twice a day for 120 minutes on each side (right and left).

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: February 7, 2022
• Study Start: May 2, 2022
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: July 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)